eda_dataset_noise.ipynb

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      "Found cached dataset json (/home/lyf6/.cache/huggingface/datasets/json/default-9ba730f179d68666/0.0.0/e347ab1c932092252e717ff3f949105a4dd28b27e842dd53157d2f72e276c2e4)\n"
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      "Found cached dataset json (/home/lyf6/.cache/huggingface/datasets/json/default-9a0418f804e277a7/0.0.0/e347ab1c932092252e717ff3f949105a4dd28b27e842dd53157d2f72e276c2e4)\n"
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   "source": [
    "import argparse\n",
    "import evaluate\n",
    "\n",
    "from datasets import load_dataset\n",
    "from fuzzywuzzy import fuzz, process\n",
    "from rank_bm25 import BM25Okapi\n",
    "from utils_eval import compute_metrics\n",
    "\n",
    "rouge = evaluate.load('rouge')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Experiment to Check % of Noise in Original Labels"
   ]
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   "source": [
    "# Get dataset from arguments\n",
    "\n",
    "DATASET_NAME = \"cochrane_full\"\n",
    "\n",
    "dataset = load_dataset(\n",
    "    \"json\", data_files=f\"data/{DATASET_NAME}_multiple.json\", field=\"train\"\n",
    ")\n",
    "dataset[\"test\"] = load_dataset(\n",
    "    \"json\", data_files=f\"data/{DATASET_NAME}_multiple.json\", field=\"test\"\n",
    ")[\"train\"]"
   ]
  },
  {
   "cell_type": "code",
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     "text": [
      "Idx 1\n",
      "Two trials met the inclusion criteria. One compared 2% ketanserin ointment in polyethylene glycol (PEG) with PEG alone, used twice a day by 40 participants with arterial leg ulcers, for eight weeks or until healing, whichever was sooner. One compared topical application of blood-derived concentrated growth factor (CGF) with standard dressing (polyurethane film or foam); both applied weekly for six weeks by 61 participants with non-healing ulcers (venous, diabetic arterial, neuropathic, traumatic, or vasculitic). Both trials were small, reported results inadequately, and were of low methodological quality. Short follow-up times (six and eight weeks) meant it would be difficult to capture sufficient healing events to allow us to make comparisons between treatments. One trial demonstrated accelerated wound healing in the ketanserin group compared with the control group. In the trial that compared CGF with standard dressings, the number of participants with diabetic arterial ulcers were only reported in the CGF group (9/31), and the number of participants with diabetic arterial ulcers and their data were not reported separately for the standard dressing group. In the CGF group, 66.6% (6/9) of diabetic arterial ulcers showed more than a 50% decrease in ulcer size compared to 6.7% (2/30) of non-healing ulcers treated with standard dressing. We assessed this as very-low certainty evidence due to the small number of studies and arterial ulcer participants, inadequate reporting of methodology and data, and short follow-up period. Only one trial reported side effects (complications), stating that no participant experienced these during follow-up (six weeks, low-certainty evidence). It should also be noted that ketanserin is not licensed in all countries for use in humans. Neither study reported time to ulcer healing, patient satisfaction or quality of life. There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers.\n",
      "We found two small studies that presented data for 49 participants with arterial leg ulcers (search conducted January 2019). The studies also included participants with other kinds of ulcers, and it is not clear what proportion of participants were diabetic. Neither study described the methods fully, both presented limited results for the arterial ulcer participants, and one study did not provide information on the number of participants with an arterial ulcer in the control group. The follow-up periods (six and eight weeks) were too short to measure healing. Therefore, the data that were available were incomplete and cannot be generalised to the greater population of people who suffer from arterial leg ulcers. One study randomised participants to either 2% ketanserin ointment in polyethylene glycol (PEG) or PEG alone, administered twice a day over eight weeks. This study reported increased wound healing in the ketanserin group, when compared with the control group. It should be noted that ketanserin is not licensed for use in humans in all countries. The second study randomised participants to either topically-applied growth factors isolated from the participant's own blood (concentrated growth factors (CGF)), or standard dressing; both applied weekly for six weeks. This study reported that 66.6% of CGF-treated diabetic arterial ulcers showed more than a 50% decrease in ulcer size, compared to 6.7% of non-healing ulcers treated with standard dressing. Only one study mentioned side effects, and reported that no participant experienced side effects during follow-up (six weeks). Neither of the two studies reported time to ulcer healing, patient satisfaction or quality of life measures. There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers. We downgraded the overall certainty of the available evidence to 'very low' and 'low', because the studies reported their methods poorly, there were only two studies and few participants with arterial disease, and because the studies were short and reported few results. This made it impossible to determine whether there was any real difference in the number of ulcers healed between the groups.\n",
      "\n",
      "\n",
      "Idx 2\n",
      "We identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of the last symptomatic event. The overall quality of the evidence was very low, due to the small number of participants from only one trial, and missing outcome data. We found no statistically significant difference between the effects of very early or delayed surgery in reducing the combined risk of stroke and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval (CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality evidence). To date, no results are available to confirm the optimal timing for surgery. There is currently no high-quality evidence available to support either very early or delayed cerebral revascularization after a recent ischemic stroke. Hence, further randomized trials to identify which patients should undergo very urgent revascularization are needed. Future studies should stratify participants by age group, sex, grade of ischemia, and degree of stenosis. Currently, there is one ongoing RCT that is examining the timing of cerebral revascularization.\n",
      "The searches are up-to-date to 26 January 2016. We found only one randomized trial that assessed the effect of the timing of surgery. It included a total of 40 participants, ranging in age from 47 to 84 years. From the limited evidence available, we cannot tell if the timing of surgery is an important factor in determining the outcome for individuals with recent symptoms from carotid artery narrowing. There is not enough evidence on the best time for surgical treatment for people with recent symptoms from carotid artery narrowing. The overall quality of the evidence was very low, due to the small number of participants from only one trial and missing outcome data. Further studies with a larger number of patients are needed.\n",
      "\n",
      "\n",
      "Idx 3\n",
      "We included 13 studies with a total of 721 participants in the review. The studies were observational, 12 studies had only one relevant treatment arm and no control and for the one study with a control arm, very few details were given. The risk of bias was high and the certainty of evidence was graded as very low for all outcomes. Due to heterogeneity of data, meta-analysis was not performed and therefore the data were synthesised via a narrative summary. The evidence for benefit derived from PN was very low for survival and quality of life. All the studies measured overall survival and 636 (88%) of participants were deceased at the end of the study. However there were varying definitions of overall survival that yielded median survival intervals between 15 to 155 days (range three to 1278 days). Three studies used validated measures of quality of life. The results from assessment of quality of life were equivocal; one study reported improvements up until three months and two studies reported approximately similar numbers of participants with improvements and deterioration. Different quality of life scales were used in each of the studies and quality of life was measured at different time points. Due to the very low certainty of the evidence, we are very uncertain about the adverse events related to PN use. Adverse events were measured by nine studies and data for individual participants could be extracted from eight studies. This revealed that 32 of 260 (12%) patients developed a central venous catheter infection or were hospitalised because of complications related to PN. We are very uncertain whether HPN improves survival or quality of life in people with MBO as the certainty of evidence was very low for both outcomes. As the evidence base is limited and at high risk of bias, further higher-quality prospective studies are required.\n",
      "The benefits of PN are uncertain as the evidence is of very low certainty, provided mainly by studies that only looked at people who received PN rather than comparing patients who received PN with those who did not. As we found no randomised controlled trials, we have included the results from 13 observational studies with a total of 721 participants. For 12 of the studies, there was only one relevant treatment group and no control group. Therefore, the results are only for people receiving PN and we have no information about those not receiving it. The average survival time for people on PN varied from three to 1278 days. Only three studies measured quality of life using a recognised measure. One study found quality of life improved and two studies found similar numbers of people both improved and deteriorated. However, the three studies monitored quality of life at different points in time and measured it in different ways. Side effects occurred in 12% of people in the eight studies that measured them. Further research is needed to find out if PN is of benefit to people with an inoperable blockage of the bowel caused by advanced cancer.\n",
      "\n",
      "\n",
      "Idx 4\n",
      "We included 25 RCTs involving 4788 participants. Six of twelve trials showed that written information significantly improved knowledge about a medicine, compared with no written information. The inability to combine results means we cannot conclude whether written information was effective for increasing knowledge. The results for attitudinal and behavioural outcomes were mixed. No studies showed an adverse effect of medicines information. The combined evidence was not strong enough to say whether written medicines information is effective in changing knowledge, attitudes and behaviours related to medicine taking. There is some evidence that written information can improve knowledge. The trials were generally of poor quality, which reduces confidence in the results. Trials examining the effects of written information need to be better designed and use consistent and validated outcome measures. Trials should evaluate internet-based medicines information. It is imperative that written medicines information be based on best practice for its information design and content, which could improve its effectiveness in helping people to use medicines appropriately.\n",
      "The findings of this review were inconclusive for a number of reasons. First, because the included trials measured different outcomes in different ways, we were unable to combine their results. Second, these trials presented the written information for patients in different ways, and most did not design the leaflets in a way that made them easy to read. Third, in many cases trials were not clearly reported, so we do not know if they were carried out correctly. Despite these limitations several trials, while using different types of information and different measures, found written information improved knowledge. This is encouraging for people who want to learn about their medicines from leaflets. None of the studies showed that written information was harmful. Future research needs to use improved methods, and needs to examine the same measures on many occasions. It is important that medicines information be well written and designed to maximise the possibility of improving knowledge. Consumers are increasingly seeking out health information, including information about medicines, on the internet, but we found no trials examining whether internet-based medicines information changed people's knowledge, attitudes, or behaviour.\n",
      "\n",
      "\n",
      "Idx 5\n",
      "We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated the evidence as moderate quality for overall survival and low quality for all other outcomes. One trial compared combined extrapleural pneumonectomy (EPP) plus neoadjuvant platinum-based chemotherapy plus postoperative high-dose hemithoracic radiotherapy with combined EPP plus platinum-based chemotherapy. The other trial compared EPP plus postoperative hemithoracic radiotherapy with standard (non-radical) therapy alone following platinum-based chemotherapy (patients in the standard therapy arm received continued oncological management according to local policy, which could include further chemotherapy or palliative radiotherapy). For the first trial, median overall survival calculated from registration was 20.8 months (95% confidence interval (CI) 14.4 to 27.8) in the no-radiotherapy group and 19.3 months (95% CI 11.5 to 21.8) in the radiotherapy group. For the second trial, median overall survival was 14.4 months (95% CI 5.3 to 18.7) for patients allocated to EPP and 19.5 months (95% CI 13.4 to time not yet reached) for patients randomised to standard non-radical therapy. In the second trial, 12 serious adverse events were reported during the study period: ten in the EPP group and two in the non-radical therapy group. Overall health-related quality of life scores were not different between the two arms in either study. We could not perform a meta-analysis of the two included trials due to clinical heterogeneity. We also identified three ongoing trials evaluating the topic of our review. The overall strength of the evidence gathered in this review is low and there is a lack of available evidence to support the use of radical multimodality therapy in routine clinical practice (particularly as one trial suggests greater harm). Given the added cost of multimodality treatment and the possible increase in risk of adverse effects, the lack of evidence of their effectiveness probably means that these interventions should currently be limited to clinical trials alone.\n",
      "We searched published medical articles to find research papers that looked at combined treatment strategies with surgery for treating people with primary pleural cancer. We looked for randomised clinical trials (where people were allocated at random to one of two or more treatments groups) and used information from those we found to form our conclusions. We found evidence up to 21 March 2017. The review authors found two small randomised clinical trials, in which a total of 104 people with pleural mesothelioma were randomised. One trial compared the addition of surgery and radiotherapy to chemotherapy with chemotherapy alone. The other trial compared the addition of radiotherapy to chemotherapy and surgery with chemotherapy and surgery alone. These two small trials suggested that there is no added value for either radiotherapy or combined radiotherapy and surgery. We could not combine the data from the trials as we had intended, because the two trials were too different. We rated the quality of evidence as moderate for survival and low quality for all the other outcomes studied. The review authors identified three ongoing randomised clinical trials, the results of which have not been published yet. We only found two relevant trials. Both were small, which made the results uncertain. It is not clear whether giving a combination of surgery and radical radiotherapy after chemotherapy is better than giving chemotherapy alone. Radical radiotherapy does not seem to improve the results of surgery alone.\n",
      "\n",
      "\n",
      "Idx 6\n",
      "Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials. One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge, whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The rate of seroconversion detected during the study did not differ between groups (risk ratio (RR) 1.70, 95% confidence interval (CI) 0.56 to 5.21; participants = 3949; studies = one, low quality evidence). The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy. No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.\n",
      "This review included two randomized controlled trials (involving 5455 women). Data could not be combined because each trial measured effectiveness in different ways. One study was from Canada and involved 432 women randomly assigned to a 10-minute presentation during a prenatal class about toxoplasmosis prevention or to a usual prenatal class. Losses to follow-up were high and 285 completed the post-test questionnaire in the third trimester. Only 5% of the intervention women recalled having obtained information on toxoplasmosis prevention during prenatal classes. However, the authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The other trial conducted in France involved 5023 pregnant women with no evidence of toxoplasmosis infection (seronegative) who were randomly assigned to receive a brochure and an audiotape containing information for toxoplasmosis prevention, or to a usual prenatal class. Losses to follow-up were high and 2790 completed both pre-test and post-test questionnaire on behavior (44.5% loss to follow-up), whereas 3949 women were tested for blood antibodies (22.4% loss to follow-up). Women's behavior did not change after the intervention. Similarly, the seroconversion rate did not differ between groups (13 out of 2591 women seroconverted in the intervention and four out of 1358 in the control group). Both trials were judged as having low methodological quality as assessed by the GRADE approach. This limits our confidence in the results. Evidence supporting prenatal education to prevent congenital toxoplasmosis is therefore limited.\n",
      "\n",
      "\n",
      "Idx 7\n",
      "Of 1777 potential studies evaluated, only two Randomized Control Trials (123 patients) were included. ß-interferon treatment compared to placebo did not show differences regarding the proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55 to1.43), and it was associated with a greater frequency of treatment-related adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI secondary outcome pre-specified in the protocol. This trial showed that at two years the numbers of active lesions on brain MRI scan in ß-interferon arm were significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI -2.15 to -0.45, P = 0.003); also, the number of participants with active lesions was significantly higher in placebo arm vs. ß-interferon arm at two years (RR 0.43, 95% CI 0.22 to 0.86, P = 0.02). Limited data on the effect of ß-interferon treatment on PPMS exists. Only two single-centre placebo controlled trials of interferon beta have been done. Based on this review, the included studies showed that ß-interferon treatment was not associated with reduced disability progression in PPMS patients. However, the trial population was too small to allow definitive conclusions on the efficacy of ß-interferon therapy in PPMS patients. Larger research studies need to be done in patients with PPMS in order to clarify whether ß-interferon is effective in this population.\n",
      "Among the pertinent medical literature only  two studies, comprising  a total of 123 participants,  met the criteria of the methodological quality necessary for their inclusion in this review. Taking into account  the disability progression, the analysis of the data showed that INF beta treatment in  patients with PPMS was  not associated with a reduction of  this parameter during the first two years of therapy. Adverse effects, mainly flu-like symptoms and injection site reactions, occurred frequently and were the same as  reported by the many studies on   IFN beta treatments in MS patients with different types of the disease. It is worth nothing that the patients’ population analysed was too small to allow a definitive conclusion on the efficacy of IFN beta therapy  in PPMS.\n",
      "\n",
      "\n",
      "Idx 8\n",
      "We included two randomised controlled trials (three reports) with 1674 participants, with mean age between 64.1 and 67.8 years. Follow-up ranged from 2 years to mean 4.3 years. For primary outcome measures, effect estimates from a single study showed uncertainty for the effect of NP-guided treatment on cardiovascular mortality in patients with cardiovascular risk factors and without heart failure (RR 0.33, 95% CI 0.04 to 3.17; 1 study; 300 participants; low-quality evidence). Pooled analysis demonstrated that in comparison to standard care, NP-guided treatment probably reduces the risk of cardiovascular hospitalisation (RR 0.52, 95% CI 0.40 to 0.68; 2 studies; 1674 participants; moderate-quality evidence). This corresponds to a risk of 163 per 1000 in the control group and 85 (95% CI 65 to 111) per 1000 in the NP-guided treatment group. When secondary outcome measures were evaluated, evidence from a pooled analysis showed uncertainty for the effect of NP-guided treatment on all-cause mortality (RR 0.90, 95% CI 0.60 to 1.35; 2 studies; 1354 participants; low-quality evidence). Pooled analysis indicates that NP-guided treatment probably reduces the risk of all-cause hospitalisation (RR 0.83, 95% CI 0.75 to 0.92; 2 studies; 1354 participants; moderate-quality evidence). This corresponds to a risk of 601 per 1000 in the control group and 499 (95% CI 457 to 553) per 1000 in the NP-guided treatment group. The effect estimate from a single study indicates that NP-guided treatment reduced the risk of ventricular dysfunction (RR 0.61, 95% CI 0.41 to 0.91; 1374 participants; high-quality evidence). The risk in this study's control group was 87 per 1000, compared with 53 (95% CI 36 to 79) per 1000 with NP-guided treatment. Results from the same study show that NP-guided treatment does not affect change in NP level at the end of follow-up, relative to standard care (MD -4.06 pg/mL, 95% CI -15.07 to 6.95; 1 study; 1374 participants; moderate-quality evidence). This review shows that NP-guided treatment is likely to reduce ventricular dysfunction and cardiovascular and all-cause hospitalisation for patients who have cardiovascular risk factors and who do not have heart failure. Effects on mortality and natriuretic peptide levels are less certain. Neither of the included studies were powered to evaluate mortality. Available evidence shows uncertainty regarding the effects of NP-guided treatment on both cardiovascular mortality and all-cause mortality; very low event numbers resulted in a high degree of imprecision in these effect estimates. Evidence also shows that NP-guided treatment may not affect NP level at the end of follow-up. As both trials included in our review were pragmatic studies, non-blinding of patients and practices may have biased results towards a finding of equivalence. Further studies with more adequately powered sample sizes and longer duration of follow-up are required to evaluate the effect of NP-guided treatment on mortality. As two trials are ongoing, one of which is a large multi-centre trial, it is hoped that future iterations of this review will benefit from larger sample sizes across a wider geographical area.\n",
      "Evidence in this review is current to July 2019. We included two randomised controlled trials (where participants have an equal chance of being assigned to either treatment) including 1674 adult participants who had one or more risk factors for developing CVD, which compared NP-guided treatment with standard care. We excluded patients with symptoms of heart failure. The mean age of participants varied between 64.1 and 67.8 years. Patients were followed-up for between 2 years and a mean of 4.2 years. Effects of NP-guided treatment on death due to CVD or for any other reason remain uncertain as our results were imprecise. Moderate-quality evidence suggests that NP-guided treatment probably reduces the number of hospitalisations due to cardiovascular events and due to all causes in patients with cardiovascular risk factors. We would expect that of 1000 patients who received standard care, 163 would be admitted to hospital as the result of a cardiovascular event, compared to between 65 and 111 patients who received NP-guided treatment. Out of 1000 patients with cardiovascular risk factors who received standard care, 601 would be admitted to hospital for any reason, compared to between 457 and 553 patients who received NP-guided treatment. High-quality evidence indicates that NP-guided treatment reduces the risk of ventricular dysfunction (a condition that often leads to heart failure) compared to standard care. Our results suggest that of 1000 patients with cardiovascular risk factors who received standard care, 87 would develop ventricular dysfunction, compared to between 36 and 79 patients who received NP-guided treatment. No evidence suggests that NP-guided treatment affected NP level at completion of the studies. The quality of evidence ranged from low to high across outcomes. Key reasons for concern about the quality of the evidence included risk of bias, as patients and medical staff caring for patients knew whether they were in the control or intervention group and this may have affected the care they received; some results obtained were imprecise, and it is unclear if the intervention was beneficial or harmful. As we identified only two studies that were suitable for inclusion in this review, the generalisability of the review is limited.\n",
      "\n",
      "\n",
      "Idx 9\n",
      "Three trials involving a total of 404, mainly female and older, people with displaced fractures of the distal radius were included. These failed to assess functional outcome, and only one trial reported on complications. One trial found no statistically significant differences between mechanical reduction using finger trap traction and manual reduction in anatomical outcomes. All participants of this trial were given intravenous regional anaesthesia. One trial compared a novel method of manual reduction where the non-anaesthetised patient actively provided counter-traction versus traditional manual reduction under intravenous regional anaesthesia. While participants of the novel method group suffered more, yet not intolerable, pain during the reduction procedure, the latter was shorter in duration. No differences in anatomical outcome were detected. The third study compared mechanical reduction involving a special device without anaesthesia versus manual reduction under haematoma block (local anaesthesia). Less pain during the reduction procedure was recorded for the mechanical traction group. Both methods yielded similar radiological results. Fewer participants of the mechanical traction group had signs of neurological impairment, mainly finger numbness, at five weeks but this difference was not statistically significant by one year. There was insufficient evidence from comparisons tested within randomised controlled trials to establish the relative effectiveness of different methods of closed reduction used in the treatment of displaced fractures of the distal radius in adults.\n",
      "Three randomised controlled trials involving a total of 404, mainly female and older, people with displaced fractures of the distal radius are included in this review. None of the trials assessed functional outcome, and only one trial reported on complications. Each trial compared different methods of reduction. One trial, in which all participants had intravenous regional anaesthesia, found no significant differences in anatomical outcomes between mechanical reduction using finger trap traction and manual reduction. The second trial compared two methods of manual reduction. These were a novel method of manual reduction where participants actively provided counter-traction without being given anaesthesia versus traditional manual reduction under intravenous regional anaesthesia. The participants of the novel method group suffered more but not intolerable pain during the reduction procedure, which was shorter in duration. No differences in anatomical outcome were detected. The third trial compared mechanical reduction involving a special device without anaesthesia versus manual reduction under haematoma block (local anaesthesia). Less pain during the reduction procedure was recorded for the mechanical traction group. Both methods yielded similar anatomical results. Fewer participants of the mechanical traction group had signs of neurological impairment, mainly finger numbness, at five weeks but this difference was not statistically significant by one year. The review concluded that there was not enough evidence to decide whether there was any difference between the various methods tested.\n",
      "\n",
      "\n",
      "Idx 10\n",
      "Twenty-two eligible randomised trials were identified, of which 11 were crossover trials. The trials included 1099 women with 673 receiving an adrenergic drug (phenylpropanolamine in 11 trials, midodrine in two, norepinephrine in three, clenbuterol in another three, terbutaline in one, eskornade in one and Ro 115-1240 in one). No trials included men. The limited evidence suggested that an adrenergic agonist drug is better than placebo in reducing the number of pad changes and incontinence episodes, as well as improving subjective symptoms. In two small trials, the drugs also appeared to be better than pelvic floor muscle training, possibly reflecting relative acceptability of the treatments to women but perhaps due to differential withdrawal of women from the trial groups. There was not enough evidence to evaluate the use of higher compared to lower doses of adrenergic agonists nor the relative merits of an adrenergic agonist drug compared with oestrogen, whether used alone or in combination. Over a quarter of women reported adverse effects. There were similar numbers of adverse effects with adrenergics, placebo or alternative drug treatment. However, when these were due to recognised adrenergic stimulation (insomnia, restlessness and vasomotor stimulation) they were only severe enough to stop treatment in 4% of women. There was weak evidence to suggest that use of an adrenergic agonist was better than placebo treatment. There was not enough evidence to assess the effects of adrenergic agonists when compared to or combined with other treatments. Further larger trials are needed to identify when adrenergics may be useful. Patients using adrenergic agonists may suffer from minor side effects, which sometimes cause them to stop treatment. Rare but serious side effects, such as cardiac arrhythmias and hypertension, have been reported.\n",
      "This review of 22 trials involving 673 women and seven different adrenergic drugs found weak evidence that adrenergic agonists may help stress urinary incontinence. Side effects do occur but are usually minor. Rarely, more serious adverse effects such as high blood pressure can occur. More evidence is needed to compare adrenergic drugs with other drugs for stress incontinence and also with pelvic floor muscle exercises.\n",
      "\n",
      "\n",
      "Idx 11\n",
      "Six studies met the inclusion criteria, including three RCTs, two cluster-RCTs and one ITS. All were conducted in the USA and comprised targeted mass media interventions for people of African descent (four studies), Spanish-language dominant Latino immigrants (one study), and Chinese immigrants (one study). The two latter studies offered the intervention in the participants’ first language (Spanish, Cantonese, or Mandarin). Three interventions targeted towards women only, one pregnant women specifically. We judged all studies as being at unclear risk of bias in at least one domain and three studies as being at high risk of bias in at least one domain. We categorised the findings into three comparisons. The first comparison examined mass media interventions targeted at ethnic minorities versus an equivalent mass media intervention intended for the general population. The one study in this category (255 participants of African decent) found little or no difference in effect on self-reported behavioural change for smoking and only small differences in attitudes to change between participants who were given a culturally specific smoking cessation booklet versus a booklet intended for the general population. We are uncertain about the effect estimates, as assessed by the GRADE methodology (very low quality evidence of effect). No study provided data for indicators of behavioural change or adverse effects. The second comparison assessed targeted mass media interventions versus no intervention. One study (154 participants of African decent) reported effects for our primary outcomes. Participants in the intervention group had access to 12 one-hour live programmes on cable TV and received print material over three months regarding nutrition and physical activity to improve health and weight control. Change in body mass index (BMI) was comparable between groups 12 months after the baseline (low quality evidence). Scores on a food habits (fat behaviours) and total leisure activity scores changed favourably for the intervention group (very low quality evidence). Two other studies exposed entire populations in geographical areas to radio advertisements targeted towards African American communities. Authors presented effects on two of our secondary outcomes, use of health promotion services and project costs. The campaign message was to call smoking quit lines. The outcome was the number of calls received. After one year, one study reported 18 calls per estimated 10,000 targeted smokers from the intervention communities (estimated target population 310,500 persons), compared to 0.2 calls per estimated 10,000 targeted smokers from the control communities (estimated target population 331,400 persons) (moderate quality evidence). The ITS study also reported an increase in the number of calls from the target population during campaigns (low quality evidence). The proportion of African American callers increased in both studies (low to very low quality evidence). No study provided data on knowledge and attitudes for change and adverse effects. Information on costs were sparse. The third comparison assessed targeted mass media interventions versus a mass media intervention plus personalised content. Findings are based on three studies (1361 participants). Participants in these comparison groups received personal feedback. Two of the studies recorded weight changes over time. Neither found significant differences between the groups (low quality evidence). Evidence on behavioural changes, and knowledge and attitudes typically found some effects in favour of receiving personalised content or no significant differences between groups (very low quality evidence). No study provided data on adverse effects. Information on costs were sparse. The available evidence is inadequate for understanding whether mass media interventions targeted toward ethnic minority populations are more effective in changing health behaviours than mass media interventions intended for the population at large. When compared to no intervention, a targeted mass media intervention may increase the number of calls to smoking quit line, but the effect on health behaviours is unclear. These studies could not distinguish the impact of different components, for instance the effect of hearing a message regarding behavioural change, the cultural adaptation to the ethnic minority group, or increase reach to the target group through more appropriate mass media channels. New studies should explore targeted interventions for ethnic minorities with a first language other than the dominant language in their resident country, as well as directly compare targeted versus general population mass media interventions.\n",
      "We found six studies, all from the USA, four of which targeted African Americans and two which targeted Latino or Chinese immigrants. Of the studies, four were experimental (1693 volunteers) and two reported the results of large, targeted campaigns run in whole communities and cities. The evidence is current to August 2016. The available evidence is insufficient to conclude whether targeted mass media interventions for ethnic minority groups are more, less or equally effective in changing health behaviours than general mass media interventions. Only one study compared participants' smoking habits and intentions to quit following the receipt of either a culturally adapted smoking advice booklet or a booklet developed for the general population. They found little or no differences in smoking behaviours between the groups. When compared to no mass media intervention, a targeted mass media intervention may increase the number of calls to smoking quit lines, but the effect on health behaviours is unclear. This conclusion is based on findings from three studies. One study gave participants access to a series of 12 live shows on cable TV with information on how to maintain a healthy weight through diet and physical activity. Compared to women who did not watch the shows, participants reported slightly increased physical activity and some positive changes to their dietary patterns; however, their body weight was no different over time. Two other studies were large-scale targeted campaigns in which smokers were encouraged to call a quit line for smoking cessation advice. The number of telephone calls from the target population increased considerably during the campaign. This review also compared targeted mass media interventions versus mass media interventions with added personal interactions. These findings, based on three studies, were inconclusive. None of the studies reported whether the interventions could have had any adverse effects, such as possible stigmatisation or increased resistance to messages. Further studies directly comparing targeted mass media interventions with general mass media interventions would be useful. Few studies have investigated the effects of targeted mass media interventions for ethnic minority groups who primarily speak a non-dominant language. Our confidence in the evidence of effect on all main outcomes is low to very low. This means that the true effect may be different or substantially different from the results presented in this review. We have moderate confidence in the estimated increase in the number of calls to smoking quit lines.\n",
      "\n",
      "\n",
      "Idx 12\n",
      "We identified six new trials for this update. In total, the evidence for this review rests on 14 trials (805 participants). Music listening was the main intervention used, and 13 of the studies did not include a trained music therapist. Results indicated that music listening may be beneficial for anxiety reduction in mechanically ventilated patients. Specifically, music listening resulted, on average, in an anxiety reduction that was 1.11 standard deviation units greater (95% CI -1.75 to -0.47, P = 0.0006) than in the standard care group. This is considered a large and clinically significant effect. Findings indicated that listening to music consistently reduced respiratory rate and systolic blood pressure, suggesting a relaxation response. Furthermore, one large-scale study reported greater reductions in sedative and analgesic intake in the music listening group compared to the control group, and two other studies reported trends for reduction in sedative and analgesic intake for the music group. One study found significantly higher sedation scores in the music listening group compared to the control group. No strong evidence was found for reduction in diastolic blood pressure and mean arterial pressure. Furthermore, inconsistent results were found for reduction in heart rate with seven studies reporting greater heart rate reductions in the music listening group and one study a slightly greater reduction in the control group. Music listening did not improve oxygen saturation levels. Four studies examined the effects of music listening on hormone levels but the results were mixed and no conclusions could be drawn. No strong evidence was found for an effect of music listening on mortality rate but this evidence rested on only two trials. Most trials were assessed to be at high risk of bias because of lack of blinding. Blinding of outcome assessors is often impossible in music therapy and music medicine studies that use subjective outcomes, unless the music intervention is compared to another treatment intervention. Because of the high risk of bias, these results need to be interpreted with caution. No studies could be found that examined the effects of music interventions on quality of life, patient satisfaction, post-discharge outcomes, or cost-effectiveness. No adverse events were identified. This updated systematic review indicates that music listening may have a beneficial effect on anxiety in mechanically ventilated patients. These findings are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. The review furthermore suggests that music listening consistently reduces respiratory rate and systolic blood pressure. Finally, results indicate a possible beneficial impact on the consumption of sedatives and analgesics. Therefore, we conclude that music interventions may provide a viable anxiety management option to mechanically ventilated patients.\n",
      "We included 14 controlled trials involving 805 critically ill participants on mechanical ventilation. All participants were alert. Slightly more patients (58%) included in these studies were male and their average age was 58 years. The majority of the studies examined the effects of patients listening to pre-recorded music. Most studies offered one 20 to 30-minute music session to the participants. The findings suggest that music listening may have a large anxiety-reducing effect on mechanically ventilated patients. The results furthermore suggest that music listening consistently reduces respiratory rate and systolic blood pressure, suggesting a relaxation response. No evidence of effect was found for diastolic blood pressure, mean arterial pressure, or oxygen saturation level and inconsistent results were found for heart rate and hormone levels. One large-scale study reported greater reductions in the intake of sedative and analgesic medications in the music listening group compared to the control group, and two other studies reported similar trends. Music listening did not result in any harm. Most trials presented some methodological weakness. Therefore, these results need to be interpreted with caution. However, the results are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable anxiety management option to mechanically ventilated patients.\n",
      "\n",
      "\n",
      "Idx 13\n",
      "We included in this updated review 33 RCTs with 3946 participants. Twenty new trials with 2780 participants had been completed since the previous review. Outcome data were available for up to 22 trials (2865 participants) that compared acupuncture with any control (open control or sham acupuncture) but for only six trials (668 participants) that compared acupuncture with sham acupuncture control. We downgraded the evidence to low or very low quality because of risk of bias in included studies, inconsistency in the acupuncture intervention and outcome measures, and imprecision in effect estimates. When compared with any control (11 trials with 1582 participants), findings of lower odds of death or dependency at the end of follow-up and over the long term (≥ three months) in the acupuncture group were uncertain (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.46 to 0.79; very low-quality evidence; and OR 0.67, 95% CI 0.53 to 0.85; eight trials with 1436 participants; very low-quality evidence, respectively) and were not confirmed by trials comparing acupuncture with sham acupuncture (OR 0.71, 95% CI 0.43 to 1.18; low-quality evidence; and OR 0.67, 95% CI 0.40 to 1.12; low-quality evidence, respectively). In trials comparing acupuncture with any control, findings that acupuncture was associated with increases in the global neurological deficit score and in the motor function score were uncertain (standardized mean difference [SMD] 0.84, 95% CI 0.36 to 1.32; 12 trials with 1086 participants; very low-quality evidence; and SMD 1.08, 95% CI 0.45 to 1.71; 11 trials with 895 participants; very low-quality evidence). These findings were not confirmed in trials comparing acupuncture with sham acupuncture (SMD 0.01, 95% CI -0.55 to 0.57; low-quality evidence; and SMD 0.10, 95% CI -0.38 to 0.17; low-quality evidence, respectively). Trials comparing acupuncture with any control have reported little or no difference in death or institutional care at the end of follow-up (OR 0.78, 95% CI 0.54 to 1.12; five trials with 1120 participants; low-quality evidence), death within the first two weeks (OR 0.91, 95% CI 0.33 to 2.55; 18 trials with 1612 participants; low-quality evidence), or death at the end of follow-up (OR 1.08, 95% CI 0.74 to 1.58; 22 trials with 2865 participants; low-quality evidence). The incidence of adverse events (eg, pain, dizziness, faint) in the acupuncture arms of open and sham control trials was 6.2% (64/1037 participants), and 1.4% of these (14/1037 participants) discontinued acupuncture. When acupuncture was compared with sham acupuncture, findings for adverse events were uncertain (OR 0.58, 95% CI 0.29 to 1.16; five trials with 576 participants; low-quality evidence). This updated review indicates that apparently improved outcomes with acupuncture in acute stroke are confounded by the risk of bias related to use of open controls. Adverse events related to acupuncture were reported to be minor and usually did not result in stopping treatment. Future studies are needed to confirm or refute any effects of acupuncture in acute stroke. Trials should clearly report the method of randomization, concealment of allocation, and whether blinding of participants, personnel, and outcome assessors was achieved, while paying close attention to the effects of acupuncture on long-term functional outcomes.\n",
      "We searched electronic databases and the Chinese Clinical Trial Registry up to February 2017, and two clinical trials platforms (WHO International Clinical Trials Registry Platform and Clinicaltrials.gov) up to April 2017. We included in this review 33 randomized clinical trials (RCTs) with 3946 participants. Of these, results were available for up to 22 trials (2865 participants) that compared acupuncture with any control but for only six trials (668 participants) that compared acupuncture with a sham acupuncture procedure. The effects of acupuncture in reducing death or dependency or improving neurological and movement scores at the end of follow-up, as seen in trials comparing acupuncture with any control, were not seen in trials comparing acupuncture with the more reliable control of sham acupuncture. Adverse events such as pain, dizziness, and faint were reported in 6.2% (64/1037) of participants, and 1.4% (14) of these had to discontinue acupuncture. The quality of the evidence was low or very low owing to risk of bias in the included studies and variation in the type and duration of acupuncture. Additional larger reliable research trials are required for enhanced confidence in the effects of acupuncture for acute stroke.\n",
      "\n",
      "\n",
      "Idx 14\n",
      "The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine. When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I2 = 0%; moderate quality evidence). This suggests that if 29% of women undergoing ART experience moderate or severe OHSS, the use of dopamine agonists will lower this to 7% to 14% of women. There was no evidence of a difference in live birth rate, clinical pregnancy rate, multiple pregnancy rate or miscarriage rate (very low to moderate quality evidence). However, taking dopamine agonists (especially quinagolide) may increase the incidence of adverse events such as gastrointestinal adverse effects (OR 4.54, 95% CI 1.49 to 13.84; 264 participants; 2 studies; I2 = 49%, very low quality evidence). When we compared dopamine agonist plus co-intervention with co-intervention, there was no evidence of a difference in the outcomes of moderate or severe OHSS, live birth rate, clinical pregnancy rate, miscarriage rate or adverse events. The co-interventions were hydroxyethyl starch (two RCTs) and albumin (one RCT). Cabergoline was associated with a lower risk of moderate or severe OHSS compared with human albumin (OR 0.21, 95% CI 0.12 to 0.38; 296 participants; 3 studies; I2 = 72%). However, there was no evidence of a difference between cabergoline and hydroxyethyl starch, coasting (withholding any more ovarian stimulation for a few days) or prednisolone. There was an increased clinical pregnancy rate in the cabergoline group when cabergoline was compared with coasting (OR 2.65, 95% CI 1.13 to 6.21; 120 participants; 2 studies; I2 = 0%). In other respects, there was no evidence of a difference in clinical pregnancy rate, multiple pregnancy rate or miscarriage rate between cabergoline and other active interventions. The quality of the evidence between dopamine agonist and placebo or no intervention ranged from very low to moderate, mainly due to poor reporting of study methods (mostly a lack of details on randomisation or blinding) and serious imprecision for some comparisons. Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.\n",
      "This review included 16 randomised controlled trials involving 2091 women at high risk of OHSS, which evaluated three different dopamine agonists (cabergoline, bromocriptine and quinagolide). The main outcome measures were the number of new cases (incidence) of moderate or severe OHSS and live birth rate. The evidence is current to August 2016. Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence) compared with placebo or no treatment. This suggests that if 29% of women taking placebo or no treatment have moderate or severe OHSS, between 7% and 14% of women taking dopamine agonists will have moderate or severe OHSS. For women who had a fresh embryo transferred as part of their treatment cycle, there was no evidence that dopamine agonists influenced pregnancy outcomes, but they might increase the risk of side effects, such as stomach upsets. There was no evidence of a difference between a dopamine agonist plus another active treatment versus another active treatment on incidence of moderate or severe OHSS and live birth rate. There was no evidence of a difference in OHSS rates between cabergoline and placebo treatments (e.g. hydroxyethyl starch, prednisolone or 'coasting' (withholding any more ovarian stimulation for a few days)). Cabergoline was associated with an increased clinical pregnancy rate compared with coasting. The quality of the evidence ranged from very low to moderate. Limitations included poor reporting of study methods and imprecision (too few events) for some comparisons.\n",
      "\n",
      "\n",
      "Idx 15\n",
      "Seven studies met our eligibility criteria. All were randomized controlled trials; six assigned clusters and one randomized individuals. Sample sizes for the cluster-randomized trials ranged from 2157 to 15,614; the number of clusters ranged from 18 to 70. Four trials took place in African countries, two in the USA, and one in England. Three were based mainly in schools, two were in community settings, one took place during military training, and one was clinic-based. Five studies provided data on pregnancy, either from pregnancy tests or national records of abortions and live births. Four trials assessed the incidence or prevalence of HIV and HSV-2. Three trials examined other STI. The trials showed or reported no significant difference between study groups for pregnancy or HIV, but favorable effects were evident for some STI. Two showed a lower incidence of HSV-2 for the behavioral-intervention group compared to the usual-care group, with reported adjusted rate ratios (ARR) of 0.65 (95% CI 0.43 to 0.97) and 0.67 (95% CI 0.47 to 0.97), while HIV did not differ significantly. One also reported lower syphilis incidence and gonorrhea prevalence for the behavioral intervention plus STI management compared to the usual-care group. The reported ARR were 0.58 (95% CI 0.35 to 0.96) and 0.28 (95% CI 0.11 to 0.70), respectively. Another study reported a negative effect on gonorrhea for young women in the intervention group versus the control group (ARR 1.93; 95% CI 1.01 to 3.71). The difference occurred among those with only one year of the intervention. We found few studies and little clinical evidence of effectiveness for interventions promoting condom use for dual protection. We did not find favorable results for pregnancy or HIV, and only found some for other STI. The overall quality of evidence was moderate to low; losses to follow up were high. Effective interventions for improving condom use are needed to prevent pregnancy and HIV/STI transmission. Interventions should be feasible for resource-limited settings and tested using valid and reliable outcome measures.\n",
      "Through September 2013, we did computer searches for studies of programs to improve condom use. We wrote to researchers for missing data. The studies could have various designs. The education program addressed preventing pregnancy and HIV/STI. The intervention was compared with a different program, usual care, or no intervention. The studies had a clinical outcome such as pregnancy, HIV, or STI tests. We did not use self-reports of condom use. We found seven randomized trials. Six assigned groups (clusters) and one randomized individuals. Four trials took place in African countries, two in the USA, and one in England. The studies were based in schools, community settings, a clinic, and a military training setting. Five trials examined pregnancy, four studied HIV and HSV-2 (herpes), and three assessed other STI. We found no major differences between study groups for pregnancy or HIV. Some results were seen for STI outcomes. Two studies showed fewer HSV-2 cases with the behavioral program compared to the control group. One also reported fewer cases of syphilis and gonorrhea with the behavioral program plus STI management. Another study reported a higher gonorrhea rate for the intervention group. The researchers believed the result was due to a subgroup that did not have the full program. We found little clinical effect of improving condom use. The studies provided moderate to low quality information. Losses to follow up were high. We need good programs on condom use to prevent pregnancy and HIV/STI. Programs should be useful for settings with few resources. Interventions should be tested with valid outcome measures.\n",
      "\n",
      "\n",
      "Idx 16\n",
      "Of the 2077 references identified, 24 trials were included in this review. For electrostimulation compared with no treatment this review found that electrostimulation improved some aspects of functional motor ability and some aspects of motor impairment and normality of movement. In addition, there was a significant difference in favour of no treatment compared with electrostimulation for an aspect of functional motor ability. For electrostimulation compared with placebo this review found that electrostimulation improved an aspect of functional motor ability. For electrostimulation compared with conventional physical therapy this review found that electrostimulation improved an aspect of motor impairment. There were no statistically significant differences between electrostimulation and control treatment for all other outcomes. However, these results need to be interpreted with reference to the following: (1) the majority of analyses only contained one trial; (2) variation was found between included trials in time after stroke, level of functional deficit, and dose of electrostimulation; and (3) the possibility of selection and detection bias in the majority of included trials. At present, there are insufficient robust data to inform clinical use of electrostimulation for neuromuscular re-training. Research is needed to address specific questions about the type of electrostimulation that might be most effective, in what dose and at what time after stroke.\n",
      "Electrostimulation is a potential treatment to improve recovery of movement control and functional ability after stroke but the results of this review are inconclusive. After stroke many people are unable to use their affected limbs in everyday activities such as walking, ascending/descending stairs, washing hair or opening a coffee jar. One way to improve recovery might be to train affected muscles by using electrostimulation. This review examined the findings of 24 randomised controlled trials of electrostimulation provided to improve the ability to voluntarily move the affected limb and/or use the affected limb in everyday activities. The available evidence suggests that when electrostimulation is compared to no treatment then there might be a small effect on some aspects of function in favour of electrostimulation. However, the majority of findings in favour of electrostimulation were found when it was compared to a group of stroke patients who were not receiving any treatment and for all but two of the outcomes examined there were no differences between either electrostimulation and placebo or between electrostimulation and another type of physical therapy. This review also found that there were many differences between randomised controlled trials in the types of stroke patients who were included, the doses of electrostimulation and the outcome measures used. This meant that many of the comparisons made in the review related to one randomised trial rather than two or more. In addition, the numbers of participants in trials were relatively small. The results of this review therefore need to be interpreted with caution.\n",
      "\n",
      "\n",
      "Idx 17\n",
      "Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX) , 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.94-3.33 for ACR 20, 3.57-4.76 for ACR 50 and 5.88 -12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.\n",
      "Infliximab is a relatively new disease modifying anti-rheumatic drug that inhibits tumour necrosis factor alpha. Short term (six to twelve month) studies suggest infliximab is well tolerated, and in combination with methotrexate, decreases disease activity in RA. Infliximab 3mg/kg or 10mg/kg, in combination with methotrexate, taken every 4 or 8 weeks for either 6 or 12 months, significantly improved disease activity as measured by tender and swollen joints and ACR response rates. Pain and physical function also improved compared to those taking methotrexate alone. Infliximab significantly reduced radiographic progression at 12 months.\n",
      "\n",
      "\n",
      "Idx 18\n",
      "Fifteen trials met the inclusion criteria (2284 participants, 69% males, 16% children). They were conducted in disparate malaria endemic areas, with the earlier studies conducted in Thailand (five) and India (two), and the more recent studies (eight) spread across three continents (South America, Africa, Asia). The 15 studies involved 41 treatment arms, 12 different drugs, and 28 different treatment regimens. Two studies examined P. vivax. Three-day azithromycin (AZ) monotherapy did not perform well for P. vivax or P. falciparum (Thailand: P. vivax failure rate 0.5 g daily, 56%, 95% CI 31 to 78. India: P. vivax failure rate 1 g daily,12%, 95% CI 7 to 21; P. falciparum failure rate 1 g daily, 64%, 95% CI 36 to 86.) A 1 g azithromycin and 0.6 g chloroquine combination daily for three days for uncomplicated P. falciparum infections was associated with increased treatment failure in India and Indonesia compared with the combination of sulphadoxine-pyrimethamine and chloroquine (pooled RR 2.66, 95% CI 1.25 to 5.67), and compared with the combination atovaquone-proguanil in a multicentre trial in Columbia and Surinam (RR 24.72, 95% CI 6.16 to 99.20). No increased risk of treatment failure was seen in two studies in Africa with mefloquine as the comparator drug (pooled RR 2.02, 95% CI 0.51 to 7.96, P = 0.3); the pooled RR for PCR-corrected data for the combination versus mefloquine was 1.01, 95% CI 0.18 to 5.84 (P = 1.0). An increased treatment failure risk was seen when comparing azithromycin in a dose of 1.2 to 1.5 mg in combination with artesunate (200 mg per day for three days) with artemether-lumefantrine (pooled RR 3.08, 95% CI 2.09 to 4.55; PCR-corrected pooled RR 3.63, 95% CI 2.02 to 6.52). Serious adverse events and treatment discontinuation were similar across treatment arms. More adverse events were reported when comparing the 1 g azithromycin/ 0.6 g chloroquine combination with mefloquine (pooled RR 1.20, 95% CI 1.06 to 1.36) or atovaquone-proguanil (RR 1.41, 95% CI 1.09 to1.83). Currently, there is no evidence for the superiority or equivalence of azithromycin monotherapy or combination therapy for the treatment of P. falciparum or P. vivax compared with other antimalarials or with the current first-line antimalarial combinations. The available evidence suggests that azithromycin is a weak antimalarial with some appealing safety characteristics. Unless the ongoing dose, formulation and product optimisation process results in a universally efficacious product, or a specific niche application is identified that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future for the treatment of malaria does not look promising.\n",
      "Our review of studies conducted over the past 14 years suggests that azithromycin is a relatively weak antimalarial whose efficacy depends on the drug dose and the partner drug in the combination therapy. The data suggest that, among adults, the higher doses needed to achieve an acceptable level of treatment success with malaria may be less well tolerated. Unless the ongoing product and dose optimisation process results in a universally efficacious product or identifies a specific niche application that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future as an antimalarial does not look promising.\n",
      "\n",
      "\n",
      "Idx 19\n",
      "We included two separate German studies involving a total of 518 participants. One study was undertaken in the inpatient treatment of schizophrenia and the other in the treatment of people newly diagnosed with depression in primary care. Regarding the primary outcomes, one study reported statistically significant increases in patient satisfaction, the other study did not. There was no evidence of effect on clinical outcomes or hospital readmission rates in either study. Regarding secondary outcomes, there was an indication that interventions to increase shared decision making increased doctor facilitation of patient involvement in decision making, and did not increase consultation times. Nor did the interventions increase patient compliance with treatment plans. Neither study reported any harms of the intervention. Definite conclusions cannot be drawn, however, on the basis of these two studies. No firm conclusions can be drawn at present about the effects of shared decision making interventions for people with mental health conditions. There is no evidence of harm, but there is an urgent need for further research in this area.\n",
      "We conducted thorough searches for randomised controlled trials (RCTs), quasi-randomised controlled trials (q-RCTs), controlled before-and-after studies (CBAs); and interrupted time series (ITS) studies of interventions to increase shared decision making in people with mental health conditions. We found two studies that met the inclusion criteria. Both studies were of good quality and made attempts to reduce potential sources of bias. We examined whether interventions to increase shared decision making affected patient satisfaction with treatment or care, led to better health outcomes or to patients being less likely to be readmitted to hospital. One of the studies indicated that the intervention increased patient satisfaction in the short term. One study indicated that doctor facilitation of consumer involvement in decision making was increased by the intervention, but no effects were found on the clinical or health service outcomes in either study. Neither study reported that shared decision making for people with mental health conditions is harmful. However, no firm conclusions can be drawn from these two studies on any of the outcomes measured and further research is needed.\n",
      "\n",
      "\n",
      "Idx 20\n",
      "As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision. NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.\n",
      "Authors search medical databases and identified 19 randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) with 759 women that could be included in the review, but data from only nine trials were suitable for analyses. Women sought help for HMB when it affected their quality of life. Levels of prostaglandin (a naturally occurring hormone) are higher in women with HMB and are reduced by NSAIDs. The review of trials found that NSAIDs were modestly effective in reducing HMB, but other medicines, such as danazol, tranexamic acid and levonorgestrel-releasing intrauterine system (LNG IUS), are more effective. These results were based on a small number of low- to moderate-quality trials. The evidence quality ranged from low to moderate, the main limitations being poor reporting of study methods and imprecision resulting from small study numbers.\n",
      "\n",
      "\n",
      "Idx 21\n",
      "We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators. None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size. For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain-free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence). Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events. The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events. Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.\n",
      "In October 2015, we searched the medical literature and found 23 studies involving 8079 participants looking at paracetamol for frequent episodic tension-type headache. About 6000 participants were involved in comparisons between paracetamol 1000 mg and placebo (a dummy tablet). Results were usually reported two hours after taking the medicine or placebo. The International Headache Society recommends the outcome of being pain free two hours after taking a medicine, but other outcomes are also suggested. Few studies reported pain free at two hours or other outcomes, so there was limited information to analyse for some outcomes. The outcome of being pain free at two hours was reported by 24 in 100 people taking paracetamol 1000 mg, and in 19 out of 100 people taking placebo, meaning that only 5 in 100 people benefited because of paracetamol 1000 mg (high quality evidence). The outcome of being pain free or having only mild pain at two hours was reported by 59 in 100 people taking paracetamol 1000 mg, and in 49 out of 100 people taking placebo (high quality evidence), meaning that only 10 in 100 people benefited because of paracetamol 1000 mg. About 10 in 100 people taking paracetamol 1000 mg reported having a side effect, which was the same as with placebo (9 in 100 people) (high quality evidence). Most side effects were mild or moderate in intensity. No side effects were serious. We found a very small amount of information comparing paracetamol 500 mg or 650 mg with placebo, and comparing paracetamol 1000 mg with other painkillers. There was no difference between any of these treatments. The quality of the evidence was moderate or high for paracetamol 1000 mg compared with placebo, and low or very low for paracetamol 500 mg to 650 mg compared with placebo, and for paracetamol 1000 mg compared with other painkillers. High quality evidence means that we are very certain about the results. Low quality evidence means that we are very uncertain about the results.\n",
      "\n",
      "\n",
      "Idx 22\n",
      "Ten relevant RCTs with 675 participants are included in this review. All trials were double blind except one single blind. All studies had a run-in phase to confirm they did not respond to their initial antipsychotic treatment. The trials were published between 1980 and 2016. In most studies the methods of randomisation, allocation and blinding were poorly reported. In addition sample sizes were often small, limiting the overall quality of the evidence. Overall, no clear difference was found between groups in terms of the number of participants who showed clinically relevant response (RR 1.09, 95% CI 0.86 to 1.40, 9 RCTs, N = 533, low-quality evidence), or left the study early due to adverse effects (RR 1.63, 95% CI 0.52 to 5.07, very low quality evidence), or due to any reason (RR 1.30, 95% CI 0.89 to 1.90, 5 RCTs, N = 353, low-quality evidence). Similarly, no clear difference was found in general mental state as measured by PANSS total score change (MD −1.44, 95% CI −6.85 to 3.97, 3 RCTs, N = 258, very low quality evidence). At least one adverse effect was equivocal between groups (RR 0.91, 95% CI 0.55 to 1.50, 2 RCTs, N = 191, very low quality evidence). Data were not reported for time in hospital or quality-of-life outcomes. Finally, subgroup and sensitivity analyses did not show any effect on the primary outcome but these analyses were clearly underpowered. Current data do not show any clear differences between increasing or maintaining the antipsychotic dose for people with schizophrenia who do not respond to their initial antipsychotic treatment. Adverse effect reporting was limited and poor. There is an urgent need for further trials in order to determine the optional treatment strategy in such cases.\n",
      "The Information Specialist of Cochrane Schizophrenia ran an electronic search of their specialised register up to 30 March 2017 for trials that randomised people with schizophrenia who were not responding to their initial antipsychotic treatment to receive either an increased antipsychotic dose or continue on the same dose. The search returned 1919 records, which were checked for eligibility by the review authors. Ten trials met the review requirements and provided usable data. No clear difference between increasing the dose of the antipsychotic drug and continuing antipsychotic treatment at the same dose was shown for any efficacy (clinical response) or safety (incidence of adverse effects) outcomes. The evidence currently available is limited and of low or very low quality. In particular, very few studies reported adverse effects adequately. The results of the present review show that there is no good-quality evidence to support or refute the hypothesis that increasing the antipsychotic dose for patients not responding to their initial antipsychotic treatment differs from continuing antipsychotic treatment at the same dose. No clear evidence regarding safety is available. Therefore, no firm conclusions can be made. Larger, well-designed trials are needed.\n",
      "\n",
      "\n",
      "Idx 23\n",
      "One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias. We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001). There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.\n",
      "The review included 13 studies with 512 adults and children with cystic fibrosis; in all of them treatment lasted for four weeks. Studies compared different formulations of pancreatic enzyme supplements, so we could not combine many of the results. Also the design of 12 of the studies meant that those taking part received both types of supplement for four weeks each, although the order in which they received them was chosen at random. This also made it difficult to analyse the results. Most of the studies were old; the most recent was from 2015, but the oldest was from 1986. We could only combine data from two small studies where individuals took miniature drug capsules (microspheres), which were treated so that the release of the medication is delayed until they have passed from the stomach into the intestine, and normal size tablets which were treated in the same way. The results did not clearly favour one or the other treatment for any of our most important outcomes (weight, height or body mass index). However, those taking the delayed-release microspheres had less fat in their feces than those taking delayed release tablets (normal size) as well as having less abdominal pain and not needing to go to the toilet as often. In a different study, those people taking the delayed-release microspheres also had less fat in their feces than those taking supplements that weren't treated so the release of medication was delayed. We didn't find any evidence that one type of these enteric-coated microspheres was better than another; or that enteric-coated microspheres were better than enteric-coated mini-microspheres (which are smaller). We didn't find any evidence on different doses of enzymes needed for people who produce different levels of pancreatic enzymes, on the best time for individuals to start treatment and different amounts of supplements based on differences in type of food eaten and meal sizes. A properly designed sudy is needed to answer these questions. We could not be sure that the people in the included studies had equal chances of being put into the different treatment groups as no details were published about how the decisions were made. Several studies also had large numbers of individuals who dropped out and often reasons for this were not given. In most studies, people took one treatment and then after a while swapped to the alternative treatment; we could only combine results from two studies which were designed in this way, and that design means that the results may seem to be more consistent than they really are when we analyse them. Finally, several studies did not completely report their findings in a way we could analyse in this review. We are not sure how these factors affect our confidence in the results we found.\n",
      "\n",
      "\n",
      "Idx 24\n",
      "We identified and included five eligible trials with a total of 167 patients. The investigators administered various G-CSF preparations, at different doses and for different durations of time. Adding G-CSF did not significantly affect the likelihood of resolution of infection or wound healing, but it was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.38; 95 % CI 0.21 to 0.70), including amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the duration of hospital stay (MD -1.40 days; 95% CI -2.27 to -0.53 days), but did not significantly affect the duration of systemic antibiotic therapy (MD -0.27 days; 95% CI -1.30 to 0.77 days). The available evidence is limited, but suggests that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer. However, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation. Clinicians might consider adding G-CSF to the usual treatment of diabetic foot infections, especially in patients with a limb-threatening infection, but it is not clear which patients might benefit.\n",
      "We found five trials which included a total of 167 people. The trials showed that adding G-CSF to usual therapy did not significantly affect the likelihood of the infection resolving or the improved healing of foot wounds, nor did it reduce the period of treatment with oral antibiotics. However, G-CSF does appear to reduce the need for surgical interventions, especially amputations, and the number of days spent in hospital. There are limitations to this analysis related to the variations in the people included in the studies (e.g. the severity of infection, the timing of the clinical assessment, the use of different G-CSF preparations, and for different lengths of time). Therefore caution is required in the interpretation of the findings.\n",
      "\n",
      "\n",
      "Idx 25\n",
      "Out of 14 717 citations, only one study met the inclusion criteria; an RCT conducted on homeless and high-risk youth between September 1998 and October 1999 in Portland, United States. Participants (n=351) were offered counselling and oral HIV testing and were randomised into face-to-face (n=187 participants) and telephone (n=167) notification groups. The telephone notification group had the option of receiving HIV test results either by telephone or face-to-face. Overall, only 48% (n=168) of participants received their HIV test results and post-test counselling. Significantly more participants received their HIV test results in the telephone notification group compared to the face-to-face notification group; 58% (n=106) vs. 37% (n=62) (p < 0.001). In the telephone notification group, the majority of participants who received their HIV test results did so by telephone (88%, n=93). The study could not offer information about the effectiveness of telephone HIV test notification with HIV-positive participants because only two youth tested positive and both were assigned to the face-to-face notification group. The study had a high risk of bias. We found only one eligible study. Although this study showed the use of the telephone for HIV test results notification was more effective than face-to-face delivery, it had a high-risk of bias. The study was conducted about 13 years ago in a high-income country, on a high-risk population, with low HIV prevalence, and the applicability of its results to other settings and contexts is unclear. The study did not provide information about telephone HIV test results notification of HIV positive people since none of the intervention group participants were HIV positive. We found no information about the acceptability of the intervention to patients’ and providers’, its economic outcomes or potential adverse effects. There is a need for robust evidence from various settings on the effectiveness of telephone use for HIV test results notification.\n",
      "The aim of this review was to assess effectiveness of the telephone for HIV test result delivery, compared with face-to-face or other methods of HIV test result notification. After a comprehensive search of various scientific databases and other resources, we found only one relevant study. This study was performed in 1998-1999 in the United States on high-risk and homeless youth. The participants were offered an HIV test and told that their HIV test results would be available in two weeks. They were then divided into two groups; one that had to return to the testing site to get their HIV test results, and another that had the option of receiving HIV test results either by telephone or face-to-face at the testing site. Overall, less than half of participants received their HIV test results. Most participants in the telephone notification group opted for telephone rather than in person delivery of HIV test results.The proportion of youth receiving their HIV test results in the telephone group was significantly higher compared to the face-to-face group. However, since none of the participants in the telephone group were HIV positive, the study could not provide information about the effectiveness of telephone HIV test result delivery in people with HIV. In addition, we could not find any information about other relevant outcomes such as participants’ and providers’ satisfaction with the telephone HIV test results delivery, cost or potential harmful effects of this intervention. We urgently need more studies conducted in various settings comparing the effectiveness of telephone to other ways of HIV test result delivery and providing other relevant information in addition to the proportion of people receiving their HIV test results.\n",
      "\n",
      "\n",
      "Idx 26\n",
      "We included three new trials in this update, which brings the total to 14 included studies that compared hypnotherapy with 22 different control interventions. The studies included a total of 1926 participants. Studies were diverse and a single meta-analysis was not possible. We judged only one study to be at low risk of bias overall; we judged 10 studies to be at high risk of bias and three at unclear risk. Studies did not provide reliable evidence of a greater benefit from hypnotherapy compared with other interventions or no treatment for smoking cessation. Most individual studies did not find statistically significant differences in quit rates after six months or longer, and studies that did detect differences typically had methodological limitations. Pooling small groups of relatively comparable studies did not provide reliable evidence for a specific effect of hypnotherapy relative to controls. There was low certainty evidence, limited by imprecision and risk of bias, that showed no statistically significant difference between hypnotherapy and attention-matched behavioural treatments (RR 1.21, 95% CI 0.91 to 1.61; I2 = 36%; 6 studies, 957 participants). Results were similarly imprecise, and also limited by risk of bias, when comparing hypnotherapy to intensive behavioural interventions (not matched for contact time) (RR 0.93, 95% CI 0.47 to 1.82; I2 = 0%; 2 studies, 211 participants; very low certainty evidence). Results from one small study (40 participants) detected a statistically significant benefit of hypnotherapy compared to no intervention (RR 19.00, 95% CI 1.18 to 305.88), but this evidence was judged to be of very low certainty due to high risk of bias and imprecision. No significant differences were detected in comparisons of hypnotherapy with brief behavioural interventions (RR 0.98, 95% CI 0.57 to 1.69; I² = 0%; 2 studies, 269 participants), rapid/focused smoking (RR 1.00, 95% CI 0.43 to 2.33; I2 = 65%; 2 studies, 54 participants), and pharmacotherapies (RR 1.68, 95% CI 0.88 to 3.20; I2 = 5%; 2 studies, 197 participants). When hypnotherapy was evaluated as an adjunct to other treatments, the pooled result from five studies showed a statistically significant benefit in favour of hypnotherapy (RR 2.10, 95% CI 1.31 to 3.35; I² = 62%; 224 participants); however, this result should be interpreted with caution due to the high risk of bias across studies (four had a high risk or bias, one had an unclear risk), and substantial statistical heterogeneity. Most studies did not provide information on whether data specifically relating to adverse events were collected, and whether or not any adverse events occurred. One study that did collect such data did not find a statistically significant difference in the adverse event ‘index’ between hypnotherapy and relaxation. There is insufficient evidence to determine whether hypnotherapy is more effective for smoking cessation than other forms of behavioural support or unassisted quitting. If a benefit is present, current evidence suggests the benefit is small at most. There is very little evidence on whether hypnotherapy causes adverse effects, but the existing data show no evidence that it does. Further large, high-quality randomized controlled trials, and more comprehensive assessments of safety, are needed on this topic.\n",
      "We found 14 studies comparing hypnotherapy with other approaches to help people stop smoking (including brief advice, or more intensive stop-smoking counselling), or no treatment. Overall, 1926 people were included. Studies lasted at least six months. The studies varied greatly in terms of the treatments they compared, so it was difficult to combine their results. We searched for evidence up to 18 July 2018. When we combined the results of six studies (with a total of 957 people) there was no evidence that hypnotherapy helped people quit smoking more than behavioural interventions, such as counselling, when delivered over the same amount of time. There was also no evidence that there was a difference between hypnotherapy and longer counselling programmes when we combined results from two studies (269 people). One study compared hypnotherapy with no treatment and found an effect in favour of hypnotherapy, but the study was small (40 people) and had issues with its methods, which means we cannot be certain about this finding. Most of the studies did not say if they also evaluated the safety of hypnotherapy. Five studies looked at adding hypnotherapy to existing treatments and found an effect, but the studies were at high risk of bias and there were large, unexplained differences in their findings. One study that compared hypnotherapy and relaxation found no difference in side effects. The evidence in this review ranges from low to very low certainty, as there was not enough information and many of the studies had issues with their designs. There is no clear evidence that hypnotherapy is better than other approaches in helping people to stop smoking. If a benefit is present, current evidence suggests the benefit is small at most. Larger, high-quality studies are needed.\n",
      "\n",
      "\n",
      "Idx 27\n",
      "We identified 12 RCTs comparing BCG versus MMC in participants with intermediate- and high-risk non-muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised. Time to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low-certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Serious adverse effects: 12/577 participants treated with BCG experienced serious non-fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low-certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Time to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low-certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency. Time to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low-certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Quality of life: we found very limited data for this outcomes and were unable to estimate an effect size. Based on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.\n",
      "The content of this review is current to September 2019. We included only studies where chance determined what treatment people in the study would get. We found 12 studies including 2932 people who matched our question. We found that BCG may lead to similar risk of dying from any cause over time (low-quality evidence), but may increase the risk of serious unwanted effects (low-quality evidence), although it is possible that it does not make a difference. BCG may reduce the risk that the tumour comes back over time (low-quality evidence), although it is possible that it does not make a difference. BCG may have little or no effect on the risk that the tumour gets worse over time (low-quality evidence). We found no data on quality of life. The quality of the evidence was consistently rated as low, meaning that our confidence is limited, and future research may change these findings.\n",
      "\n",
      "\n",
      "Idx 28\n",
      "In this update, we identified eight new studies, thereby including a total of 22 trials (2503 participants), 10 of which had a low risk of bias. Most rehabilitation programmes were assessed in only one study. Both men and women were included, and overall mean age was 41.4 years. All participants had received standard discectomy, microdiscectomy and in one study standard laminectomy and (micro)discectomy. Mean duration of the rehabilitation intervention was 12 weeks; eight studies assessed six to eight-week exercise programmes, and eight studies assessed 12 to 13-week exercise programmes. Programmes were provided in primary and secondary care facilities and were started immediately after surgery (n = 4) or four to six weeks (n = 16) or one year after surgery (n = 2). In general, the overall quality of the evidence is low to very low. Rehabilitation programmes that started immediately after surgery were not more effective than their control interventions, which included exercise. Low- to very low-quality evidence suggests that there were no differences between specific rehabilitation programmes (multidisciplinary care, behavioural graded activity, strength and stretching) that started four to six weeks postsurgery and their comparators, which included some form of exercise. Low-quality evidence shows that physiotherapy from four to six weeks postsurgery onward led to better function than no treatment or education only, and that multidisciplinary rehabilitation co-ordinated by medical advisors led to faster return to work than usual care. Statistical pooling was performed only for three comparisons in which the rehabilitation programmes started four to six weeks postsurgery: exercise programmes versus no treatment, high- versus low-intensity exercise programmes and supervised versus home exercise programmes. Very low-quality evidence (five RCTs, N = 272) shows that exercises are more effective than no treatment for pain at short-term follow-up (standard mean difference (SMD) -0.90; 95% confidence interval (CI) -1.55 to -0.24), and low-quality evidence (four RCTs, N = 252) suggests that exercises are more effective for functional status on short-term follow-up (SMD -0.67; 95% CI -1.22 to -0.12) and that no difference in functional status was noted on long-term follow-up (three RCTs, N = 226; SMD -0.22; 95% CI -0.49 to 0.04). None of these studies reported that exercise increased the reoperation rate. Very low-quality evidence (two RCTs, N = 103) shows that high-intensity exercise programmes are more effective than low-intensity exercise programmes for pain in the short term (weighted mean difference (WMD) -10.67; 95% CI -17.04 to -4.30), and low-quality evidence (two RCTs, N = 103) shows that they are more effective for functional status in the short term (SMD -0.77; 95% CI -1.17 to -0.36). Very low-quality evidence (four RCTs, N = 154) suggests no significant differences between supervised and home exercise programmes for short-term pain relief (SMD -0.76;  95% CI -2.04 to 0.53) or functional status (four RCTs, N = 154; SMD -0.36; 95% CI -0.88 to 0.15). Considerable variation was noted in the content, duration and intensity of the rehabilitation programmes included in this review, and for none of them was high- or moderate-quality evidence identified. Exercise programmes starting four to six weeks postsurgery seem to lead to a faster decrease in pain and disability than no treatment, with small to medium effect sizes, and high-intensity exercise programmes seem to lead to a slightly faster decrease in pain and disability than is seen with low-intensity programmes, but the overall quality of the evidence is only low to very low. No significant differences were noted between supervised and home exercise programmes for pain relief, disability or global perceived effect. None of the trials reported an increase in reoperation rate after first-time lumbar surgery. High-quality randomised controlled trials are strongly needed.\n",
      "This updated review evaluated the effectiveness of various rehabilitation programmes for patients who had lumbar disc surgery for the first time. We included 22 randomised controlled trials with 2503 participants, both men and women, between the ages of 18 and 65 years. The evidence is current to May 2013. Most commonly, treatment started four to six weeks after surgery, but the start of treatment ranged from two hours to 12 months after surgery. Considerable variation in the content, duration and intensity of treatments (i.e. exercise programmes) has been noted. The duration of the interventions varied from two weeks to one year; most programmes lasted six to 12 weeks. Participants reported on average serious pain intensity (56 points on a zero to 100 scale, with 100 being the worst possible pain). Most studies compared (1) exercise versus no treatment, (2) high-intensity exercise versus low-intensity exercise or (3) supervised exercise versus home exercise, most commonly starting four to six weeks after surgery. Comparisons in this review included (1) exercise versus no treatment, (2) high-intensity versus low-intensity exercise and (3) supervised versus home exercise. Patients who participated in exercise programmes four to six weeks after surgery reported slightly less short-term pain and disability than those who received no treatment. Patients who participated in high-intensity exercise programmes reported slightly less short-term pain and disability than those participating in low-intensity exercise programmes. Patients in supervised exercise programmes reported little or no difference in pain and disability compared with those in home exercise programmes. Here it was difficult to draw firm conclusions in the absence of high-quality evidence. None of the trials reported an increase in reoperation rate after first-time lumbar surgery. The evidence does not show whether all patients should be treated after surgery or only those who still have symptoms four to six weeks later. Limitations in the methods of half of the trials suggest that the results should be read with caution. Most of the treatments were assessed in only one trial. Therefore for most of the interventions, only low- to very low-quality evidence indicates that no firm conclusions can be drawn regarding their effectiveness.\n",
      "\n",
      "\n",
      "Idx 29\n",
      "We included 23 RCTs that were published between 1968 and 2015 and included 39,195 participants in total. The mean age ranged from 33 to 71 years. The median duration of treatment was 11.5 months, and the median dose of niacin was 2 g/day. The proportion of participants with prior myocardial infarction ranged from 0% (4 trials) to 100% (2 trials, median proportion 48%); the proportion of participants taking statin ranged from 0% (4 trials) to 100% (12 trials, median proportion 100%). Using available cases, niacin did not reduce overall mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.12; participants = 35,543; studies = 12; I2 = 0%; high-quality evidence), cardiovascular mortality (RR 1.02, 95% CI 0.93 to 1.12; participants = 32,966; studies = 5; I2 = 0%; moderate-quality evidence), non-cardiovascular mortality (RR 1.12, 95% CI 0.98 to 1.28; participants = 32,966; studies = 5; I2 = 0%; high-quality evidence), the number of fatal or non-fatal myocardial infarctions (RR 0.93, 95% CI 0.87 to 1.00; participants = 34,829; studies = 9; I2 = 0%; moderate-quality evidence), nor the number of fatal or non-fatal strokes (RR 0.95, 95% CI 0.74 to 1.22; participants = 33,661; studies = 7; I2 = 42%; low-quality evidence). Participants randomised to niacin were more likely to discontinue treatment due to side effects than participants randomised to control group (RR 2.17, 95% CI 1.70 to 2.77; participants = 33,539; studies = 17; I2 = 77%; moderate-quality evidence). The results were robust to sensitivity analyses using different assumptions for missing data. Moderate- to high-quality evidence suggests that niacin does not reduce mortality, cardiovascular mortality, non-cardiovascular mortality, the number of fatal or non-fatal myocardial infarctions, nor the number of fatal or non-fatal strokes but is associated with side effects. Benefits from niacin therapy in the prevention of cardiovascular disease events are unlikely.\n",
      "We found 23 studies including 39,195 participants that compared niacin to placebo. The evidence is current up to August 2016. The majority of included participants were on average 65 years old and had already experienced a myocardial infarction. The participants took niacin or placebo for a period of between six months and five years. Seventeen out of 23 studies were fully or partially funded by the drug manufacturer with a commercial interest in the results of the studies. Niacin did not reduce the number of deaths, heart attack or stroke. Many people (18%) had to stop taking niacin due to side effects. The results did not differ between participants who had or had not experienced a heart attack before taking niacin. The results did not differ between participants who were or were not taking a statin (another drug that prevents heart attack and stroke). The overall quality of evidence was moderate to high. In summary, we found no evidence of benefits from niacin therapy.\n",
      "\n",
      "\n",
      "Idx 30\n",
      "Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. Routine prophylactic stenting reduces the incidence of MUCs. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.\n",
      "This review aimed to determine the benefit and harms of the use of routine stenting in kidney transplant recipients in the prevention of urological complications. Seven studies (1154 patients) were identified. The incidence of MUCs were significantly reduced by the use of prophylactic stenting. Urinary tract infections (UTIs) were more common in stented patients however the addition of antibiotic prophylaxis resulted in no difference in the incidence of UTIs between the two groups. More studies are needed to investigate the use of selective versus universal prophylactic stenting for the unresolved issues of quality of life and cost.\n",
      "\n",
      "\n",
      "Idx 31\n",
      "One trial was eligible for inclusion.  All participants were age 60 years or over and had received a repeat prescription from their general practitioner of quinine for nighttime cramps in the preceding three months. This review includes data from only those participants who were advised to continue taking quinine. Forty-nine participants were advised to complete lean-to-wall calf muscle stretching held for 10 s three times per day. Forty-eight participants were allocated to a placebo stretching group. After 12 weeks, there was no statistically significant difference in recalled cramp frequency between groups. No \"significant\" adverse effect was reported. Limitations in the study's design impede interpretation of the results and clinical applicability. There is limited evidence on which to base clinical decisions regarding the use of non-drug therapies for the treatment of lower limb muscle cramp. Serious methodological limitations in the existing evidence hinder clinical application. There is an urgent need to carefully evaluate many of the commonly recommended and emerging non-drug therapies in well designed randomised controlled trials.\n",
      "Only one randomised trial has assessed the effectiveness of a non-drug treatment for lower limb muscle cramp. This trial evaluated day-time calf muscle stretching to prevent nighttime muscle cramp in adults age 60 years and over who had received a repeat prescription of quinine for nighttime cramps in the preceding three months. Forty-nine participants were advised to complete lean-to-wall calf muscle stretching held for 10 s three times per day. Forty-eight participants were allocated to a placebo stretching group. After 12 weeks, there was no statistically significant difference in the frequency of cramps, as recalled by the participants, between groups. No \"significant\" adverse effect was reported. Owing to serious limitations in the design of the trial, it is impossible to determine from the available evidence whether or not calf muscle stretching can prevent recurrent lower limb muscle cramp. Further research is required to determine the effectiveness of non-drug treatments for lower limb muscle cramp.\n",
      "\n",
      "\n",
      "Idx 32\n",
      "We included 12 studies (2351 participants: range 27 to 841). Characteristics: The 12 included studies compared hypertonic (colloids) with isotonic fluids (crystalloids); of these, five studies (1420 participants) also compared 0.9% saline with another fluid. No data were available to make other comparisons. Delay from stroke to recruitment varied from less than 24 hours to 72 hours. Duration of fluid delivery was between two hours and 10 days. Bias assessment: Investigators and participants in eight of the 12 included studies were blind to treatment allocation, seven of the 12 included studies gave details of randomisation, and eight of the 12 included studies reported all outcomes measured. Results: There were no relevant completed trials that addressed the effect of volume, duration, or mode of fluid delivery on death or dependence in people with stroke. The odds of death or dependence were similar in participants allocated to colloids or crystalloid fluid regimens (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.79 to 1.21, five studies, I² = 58%, low-quality evidence), and between 0.9% saline or other fluid regimens (OR 1.04, 95% CI 0.82 to 1.32, three studies, I² = 71%, low-quality evidence). There was substantial heterogeneity in these estimates. The odds of death were similar between colloids and crystalloids (OR 1.02, 95% CI 0.82 to 1.27, 12 studies, I² = 24%, moderate-quality evidence), and 0.9% saline and other fluids (OR 0.87, 95% CI 0.67 to 1.12, five studies, I² = 53%, low-quality evidence). The odds of pulmonary oedema were higher in participants allocated to colloids (OR 2.34, 95% CI 1.28 to 4.29, I² = 0%). Although the studies observed a higher risk of cerebral oedema (OR 0.20, 95% CI 0.02 to 1.74) and pneumonia (OR 0.58, 95% CI 0.17 to 2.01) with crystalloids, we could not exclude clinically important benefits or harms. We found no evidence that colloids were associated with lower odds of death or dependence in the medium term after stroke compared with crystalloids, though colloids were associated with greater odds of pulmonary oedema. We found no evidence to guide the best volume, duration, or mode of parenteral fluid delivery for people with acute stroke.\n",
      "The evidence is current to May 2015. We found 12 relevant studies (with 2351 participants) comparing colloids with crystalloids. Eleven of these studies included people with ischaemic stroke (stroke sustained due to a clot), whilst one study included people with haemorrhagic stroke (stroke due to a bleed). Five of these studies (1420 participants) also made a comparison between 0.9% saline, the most commonly prescribed iv fluid, and another fluid type. The largest study had 841 participants, whilst the smallest had 27 participants. The length of time that fluids were given varied between trials, from two hours to 10 days. Ten studies revealed a source of funding. Of these, two studies were funded by fluid manufacturers. We did not find any studies that examined the best fluid volume, mode of fluid delivery, or duration of fluid treatment. We found that people with acute stroke given crystalloids (including 0.9% saline) had about the same risk of death or dependence as people given other fluid types. People given crystalloids also had a lower risk of pulmonary oedema, a complication that can lead to breathlessness due to excess collection of watery fluid in the lungs. From the evidence we obtained, it was difficult to make any concrete conclusions about which fluids were better for reducing brain swelling (cerebral oedema) or a serious lung infection (pneumonia). We found no evidence to guide the best volume, duration, or mode of parenteral fluid delivery for people with acute stroke. The majority of studies had a low to moderate risk of bias based on study limitations and inconsistency. Most studies reported the outcomes they stated they would.\n",
      "\n",
      "\n",
      "Idx 33\n",
      "Three trials involving 5905 participants were included. In patients with mild asthma who do not need maintenance treatment, no clinically important advantages of budesonide/formoterol as reliever were found in comparison to formoterol as reliever. Two studies enrolled patients with more severe asthma who were not controlled on high doses of inhaled corticosteroids (around 700 mcg/day in adults), and had suffered a clinically important asthma exacerbation in the past year. Hospitalisations related to asthma in the two studies comparing budesonide/formoterol for maintenance and relief with the same dose of budesonide/formoterol for maintenance with terbutaline for relief yielded an odds ratio of 0.68 (95% CI 0.40 to 1.16), which was not a statistically significant reduction. In adults there was a reduction in exacerbations requiring oral corticosteroids compared to terbutaline, odds ratio 0.54 (95% CI 0.44 to 0.65), which translates into a number needed to treat over 12 months of 15 (95% CI 13 to 21). The study in children found less serious adverse events with budesonide/formoterol used for maintenance and relief. There was no significant difference in annual growth in children using budesonide/formoterol reliever in comparison to terbutaline. In mild asthma it is not yet known whether patients who use a budesonide/formoterol inhaler for relief of asthma symptoms derive any clinically important benefits. In more severe asthma, two studies enrolled patients who were not controlled on inhaled corticosteroids, and had suffered an exacerbation in the previous year, and then had their maintenance inhaled corticosteroids reduced in both arms of the study. Under these conditions the studies demonstrated a reduction in the risk of exacerbations that require oral corticosteroids with budesonide/formoterol for maintenance and relief in comparison with budesonide/formoterol for maintenance and terbutaline or formoterol for relief. The incidence of serious adverse events in children was also less using budesonide/formoterol for maintenance and relief in one study, which similarly enrolled children who were not controlled on inhaled corticosteroids, and who had their maintenance inhaled corticosteroids reduced at the start of the study. This study also compared an explorative maintenance dose of budesonide/formoterol that is not approved for treatment.\n",
      "Three trials involving 5905 participants were included. We found very little evidence in relation to the use of formoterol and budesonide for relief of symptoms in people with mild asthma, but in people with more severe asthma who had suffered exacerbations in spite of regular treatment with inhaled corticosteroids, we found that reliever formoterol and budesonide compared favourably with terbutaline in reducing asthma exacerbations that required a course of oral corticosteroids. However only a small proportion of the 'severe asthma exacerbations' as defined in the trials led to hospital admissions, and no significant overall benefit has yet been shown for this outcome. In children with asthma that was not controlled with regular inhaled corticosteroids, there were fewer serious adverse events when formoterol and budesonide were used to relieve symptoms as well as for maintenance treatment.\n",
      "\n",
      "\n",
      "Idx 34\n",
      "In this updated review four studies met the inclusion criteria. In total 366 participants were treated with lumiracoxib 400 mg, 51 with lumiracoxib 100 mg, and 212 with placebo. Active comparators were naproxen 500 mg, rofecoxib 50 mg, celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 400 mg. With lumiracoxib 400 mg 50% of participants had at least 50% pain relief over six hours, compared with 8% given placebo; RB 6.9 (95% CI 4.1 to 12), NNT 2.4 (2.1 to 2.8). Median time to onset of analgesia was shorter for lumiracoxib 400 mg (0.6 to 1.5 hours) than placebo (>12 hours). Fewer participants needed rescue medication with lumiracoxib (64%) than with placebo (91%) over 12 to 24 hours; NNT to prevent remedication 3.7 (2.9 to 5.0). The weighted median time to use of rescue medication was 9.4 hours for lumiracoxib 400 mg and 1.7 hours for placebo. Adverse events were generally mild to moderate in severity, with one serious event reported in a placebo patient. Lumiracoxib 400 mg given as a single oral dose is an effective analgesic for acute postoperative pain, and has a relatively long duration of action. Adverse events with lumiracoxib did not differ from placebo.\n",
      "Lumiracoxib 400 mg provided rapid, effective, and sustained relief of postoperative pain in four studies in dental and orthopaedic surgery. Of 366 participants treated with lumiracoxib 400 mg half experienced a high level of pain relief (at least 50% pain relief over a six hour period), compared with 8% given placebo. The duration of analgesia was relatively long at 9 hours, and fewer participants needed to use rescue medication with lumiracoxib than with placebo. Adverse event data was inconsistently reported, but no serious adverse events occurred in any patient taking lumiracoxib in these studies.\n",
      "\n",
      "\n",
      "Idx 35\n",
      "We found no evidence comparing slow-release fluoride devices against other types of fluoride therapy. We found only one double-blind RCT involving 174 children comparing a slow-release fluoride device (glass beads with fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth) against control (glass beads without fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth). This study was assessed to be at high risk of bias. The study recruited children from seven schools in an area of deprivation that had low levels of fluoride in the water. The mean age at the beginning of the study was 8.8 years and at the termination was 10.9 years. DMFT in permanent teeth or dmft in primary teeth was greater than one at the start of the study and greater than one million colony-forming units of Streptococcus mutans per millilitre of saliva. Although 132 children were still included in the trial at the two-year completion point, examination and statistical analysis was performed on only the 63 children (31 in intervention group, 32 in control group) who had retained the beads (retention rate was 47.7% at 2 years). Among these 63 children, caries increment was reported to be statistically significantly lower in the intervention group than in the control group (DMFT: mean difference -0.72, 95% confidence interval (CI) -1.23 to -0.21; DMFS: mean difference -1.52, 95% CI -2.68 to -0.36 (very low-quality evidence)). Although this difference was clinically significant, it only holds true for those children who maintain the fluoride beads; over 50% of children did not retain the beads. Harms were not reported within the trial report. Evidence for other outcomes sought in this review (progression to of caries lesion, dental pain, healthcare utilisation data) were also not reported. There is insufficient evidence to determine the caries-inhibiting effect of slow-release fluoride glass beads. The body of evidence available is of very low quality and there is a potential overestimation of benefit to the average child. The applicability of the findings to the wider population is unclear; the study had included children from a deprived area that had low levels of fluoride in drinking water, and were considered at high risk of caries. In addition, the evidence was only obtained from children who still had the bead attached at 2 years (48% of all available children); children who had lost their slow-release fluoride devices earlier might not have benefited as much from the devices.\n",
      "Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 23 January 2018. We searched scientific databases for clinical trials in children or adults treated with slow-release fluoride devices compared with another type of fluoride treatment (e.g. toothpaste, mouthrinse, gel, or varnish), placebo (a pretend treatment), or no treatment (usual care). Treatments had to be used and monitored for a minimum of 1 year. We found one study that randomised 174 children to either slow-dissolving, fluoride-releasing glass beads or placebo beads. The setting was an inner city school in an area served with low-fluoride water. Only 48% of children retained the beads and were available for analysis. There is insufficient evidence to determine whether slow-release fluoride devices (such as glass beads) help reduce dental decay. Retention of the beads is a problem. The evidence relating caries increment, side effects and retention was considered to be very low quality.\n",
      "\n",
      "\n",
      "Idx 36\n",
      "The review included six trials with a total of 361 participants. Two studies were conducted in America and one each in Germany, Greece, India, and Saudi Arabia. The participants of four trials had open-angle glaucoma; one study included participants with primary open-angle or primary closed-angle glaucoma, and one study did not specify the type of glaucoma. Three studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was performed in four studies, and trabeculectomy with 5-fluorouracil (5-FU) was performed in only one study. None of the included trials reported trabeculectomy failure at 24 months. Only one trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomised to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (risk ratio (RR) 0.33, 95% confidence interval (95% CI) 0.04 to 3.10); therefore we are very uncertain as to the relative effect of the two procedures on failure rate. Four studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95% CI −0.45 to 1.33) and 0.86 mmHg, (95% CI −0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate quality of evidence). One trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, three trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of postoperative IOP-lowering medications between the two surgical techniques. Mean difference was 0.02, (95% CI −0.15 to 0.19) at 12 months of follow-up (high quality of evidence). Because of the small numbers of events and total participants, the risk of many reported adverse events were uncertain and those that were found to be statistically significant may have been due to chance. For risk of bias assessment: although all six trials were randomised selection bias was mostly unclear, with unclear random sequence generation in four of the six studies and unclear allocation concealment in five of the six studies. Attrition bias was encountered in only one trial which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. Trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon 'performance', hence performance bias was not evaluated. The main result of this review was that there was uncertainty as to the difference between fornix- and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques.\n",
      "Six randomised controlled trials (RCTs) were reviewed with a total of 361 participants consisting of adults with any type of glaucoma and follow-up of at least 24 months. We last searched the databases on 23 October 2015. Failure rate at 24 months was not reported in any included studies, and one study reported \"late complications\" but did not specify a time period, which favoured the fornix-based treatment. No difference was noted with respect to lowering eye pressure after 24 months (two trials) and after 12 months (four trials). The number of medications needed to control eye pressure after surgery was also similar. Moreover, most of the studies reported that the complication rates after the operation were similar except in one complication which was narrowing in the anterior part of the eye after the procedure (more common in the limbal surgery group), but this did not affect the final outcome of the surgery. Although all six trials were reported to be randomised, the procedures followed for randomisation were mostly unclear (four of the six studies). Masking of the outcomes was not clear or not addressed in all six trials. Missing information was encountered in only one trial which also suffered from bias in reporting its outcomes. All other trials had an unclear risk of reporting bias as there was no access to original data.\n",
      "\n",
      "\n",
      "Idx 37\n",
      "For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis. Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear. Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained. In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite. There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.\n",
      "Our evidence is current to August 2015. We did not identify any new trials for the update of this review. The previous publication of this review included seven trials with 362 participants. Four trials compared the effect of a steroid to a placebo, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. The length of treatment varied between a single dose and a 12-day course. The doses used also varied. The length of follow-up varied from short periods (i.e. days or weeks) to longer periods (i.e. six months and 12 months). Steroid treatment relieved sore throat in the short term (at 12 hours). The researchers noticed a benefit at two to four days when steroids were used in combination with an antiviral medication, but these findings are limited since researchers assessed them in one or two trials only. The findings on the effect of steroids alone or when used with an antiviral medication for other symptoms were less clear. We are unsure about adverse effects from using steroids. With the exception of two trials, most studies did not set out a prior plan to evaluate the occurrence of side effects, or other adverse events. None of the trials explored adverse effects in the longer term (over years). The quality of the included trials was generally poor. We cannot know the exact effect of using steroids for glandular fever.\n",
      "\n",
      "\n",
      "Idx 38\n",
      "We considered twenty-four studies for inclusion in the final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention. One of these twenty studies evaluated the use of phlebotonics with a medical intervention and another study with rubber band ligation. The remaining four studies included two which compared different forms of phlebotonics with each other, one study which evaluated phlebotonics with a medical intervention and one study which compared the use of phlebotonics with infrared photocoagulation. Eight studies were excluded for various reasons including poor methodological quality. Phlebotonics demonstrated a statistically significant beneficial effect for the outcomes of  pruritus (OR 0.23; 95% CI 0.07 to 0.79) (P=0.02), bleeding (OR 0.12; 95% CI 0.04 to 0.37) (P=0.0002), bleeding post-haemorrhoidectomy (OR 0.18; 95% 0.06 to 0.58)(P=0.004), discharge and leakage (OR 0.12; 95% CI 0.04 to 0.42) (P=0.0008) and overall symptom improvement (OR 15.99 95% CI 5.97 to 42.84) (P< 0.00001), in comparison with a control intervention. Although beneficial they did not show a statistically significant effect compared with a control intervention for pain (OR 0.11; 95% CI 0.01 to 1.11) (P=0.06), pain scores post-haemorrhoidectomy (SMD -1.04; 95% CI -3.21 to 1.12 ) (P= 0.35) or post-operative analgesic consumption (OR 0.54; 95% CI 0.30 to 0.99)(P=0.05). The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease as well as a benefit in alleviating post-haemorrhoidectomy symptoms. Outcomes such as bleeding and overall symptom improvement show a statistically significant beneficial effect and there were few concerns regarding their overall safety from the evidence presented in the clinical trials. However methodological limitations were encountered. In order to enhance our conclusion further, more robust clinical trials which take into account these limitations will need to be performed in the future.\n",
      "We considered twenty four studies for inclusion in this review. This review identified twenty randomised controlled trials enrolling a total of (2334) participants which compared an intervention using phlebotonics with a control intervention. Of these twenty studies, one study compared phlebotonics with a medical intervention and another with rubber band ligation. Of the remaining four trials, we identified two trials which compared phlebotonics with each other, one trial which compared phlebotonics with herbal therapy and one trial which compared phlebotonics with infrared photocoagulation. The trials obtained did not show any significant adverse events or side-effects from the use of phlebotonics. The studies demonstrated a beneficial effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease as well as symptom relief post-haemorrhoidectomy.\n",
      "\n",
      "\n",
      "Idx 39\n",
      "We included seven trials with a total of 239 participants. Two trials were of cross-over design, and outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Thus, the results of the review are based on five trials with 213 participants. Treatment effects were observed on the following primary endpoints of emotionalism: There is very low quality of evidence from one small RCT that antidepressants increased the number of people who had 50% reduction in emotionalism (RR 16.50, 95% CI 1.07 to 253.40; 19 participants) and low quality evidence from one RCT of improved scores on Center for Neurologic Study - Lability Scale (CNS-LS) and Clinician Interview-Based Impression of Change (CIBIC) with antidepressants (RR 1.44, 95% CI 0.95 to 2.19; 28 participants). There was moderate quality evidence from three RCTS that they increased the number of people who had a reduction in tearfulness (RR 2.18, 95% CI 1.29 to 3.71; 164 participants); and low quality evidence from one RCT of improved scores on the Pathological Laughter and Crying Scale (PLCS) (MD 8.40, 95% CI 11.56 to 5.24; 28 participants). Six trials reported adverse events (death) and found no difference between the groups in death (RR 0.59, 95% CI 0.08 to 4.50; 6 RCTs, 172 participants, moderate-quality evidence). Antidepressants may reduce the frequency and severity of crying or laughing episodes based on very low quality evidence. Our conclusions must be qualified by several methodological deficiencies in the studies and interpreted with caution despite the effect being very large. The effect does not seem specific to one drug or class of drugs. More reliable data are required before appropriate conclusions can be made about the treatment of post-stroke emotionalism. Future trialists investigating the effect of antidepressants in people with emotionalism after stroke should consider developing and using a standardised method to diagnose emotionalism, determine severity and assess change over time; provide treatment for a sufficient duration and follow-up to better assess rates of relapse or maintenance and include careful assessment and complete reporting of adverse events.\n",
      "We included seven randomised controlled trials involving 239 participants in the review, which reported on the use of antidepressants for treating emotionalism. Trials ranged from small (10 participants) to large (92 participants). Mean/median age of participants ranged from 57.8 years to 73 years. Studies were from Europe (UK: 1, Denmark: 1, Scotland: 1, and Sweden: 1); Asia (South Korea: 1; and Japan: 1); and the USA: 1. We included seven trials involving 239 participants (we identified no new trials since the previous version of the review). Two trials were of cross-over design, and outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Data were only available for five trials with 213 participants. We observed treatment effects on the following: 50% reduction in emotionalism, improvements (reduction) in lability, Clinician Interview-Based Impression of Change (CIBIC), diminished tearfulness and scores on the Pathological Laughter and Crying Scale (PLCS). However, confidence intervals were wide indicating that treatment may have had only a small positive effect, or even a small negative effect (in one trial). Six trials reported death as an adverse event and found no differences between groups. We rated the evidence from very low to moderate quality due to these being small trials with some degree of bias. Antidepressant drugs appear to reduce outbursts of crying or laughing. More trials with systematic assessment and reporting of adverse events are needed to ensure that these benefits outweigh the risks.\n",
      "\n",
      "\n",
      "Idx 40\n",
      "Eleven trials, involving a total of 698 participants, were included. The trials enrolled three types of participants (high risk of failure, trabeculectomy combined with cataract surgery, no previous surgical intervention). Mitomycin C appears to reduce the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval: 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean IOP was significantly reduced at 12 months in all three participant groups receiving MMC compared to placebo. No significant increase in permanent sight-threatening complications was detected. However, none of the trials were large enough or of sufficient duration to address the long-term risk of bleb infection and endophthalmitis which has been reported in observational studies. Some evidence exists that MMC increases the risk of cataract. Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean IOP at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.\n",
      "This review asks whether there is evidence that its use during the initial stages of surgery to prevent the excessive conjunctival scarring reduces the risk of failure of the operation. Three types of patient were included: those at high risk of failure because of previous failed surgery or other complications, those having combined cataract and glaucoma surgery and those having primary trabeculectomy - an operation for the first time for their glaucoma. The review found evidence that Mitomycin C reduces the risk of surgical failure in both high risk and primary surgery but no evidence on combined cataract and glaucoma surgery. But the risk of adverse effects including an increased risk of cataracts (not in the combined group) was also noted. There were only a few studies on each category of patients and most were of only poor or moderate quality.\n",
      "\n",
      "\n",
      "Idx 41\n",
      "We included only one trial in the review. Keszler 1991 randomly assigned 166 preterm infants; reported data on 144 infants; and permitted cross-over to the alternate treatment if initial treatment failed. Investigators found no statistically significant differences in overall mortality (including survival after cross-over) between the two groups (RR 1.07, 95% confidence interval (CI) 0.67 to 1.72). In a secondary analysis of infants up to the time of cross-over, rescue treatment with HFJV was associated with lower mortality (RR 0.66, 95% CI 0.45 to 0.97). Researchers reported no significant differences in the incidence of CLD among survivors at 28 days of age, nor in the incidence of intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis. Study authors reported no significant differences in overall mortality between rescue high-frequency jet ventilation and conventional ventilation and presented highly imprecise results for important adverse effects such as intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis. The overall quality of evidence is affected by limitations in trial design and by imprecision due to the small number of infants in the included study. Existing evidence does not support the use of high-frequency jet ventilation as rescue therapy in preterm infants. Studies that target populations at greatest risk and that have sufficient power to assess important outcomes are needed. These trials should incorporate long-term pulmonary and neurodevelopmental outcomes.\n",
      "One study randomly assigned 166 preterm infants and reported data on 144 infants. The included study was completed before the introduction of surfactant and widespread use of antenatal steroids. This trial demonstrated no differences in outcomes among infants who received high-frequency jet ventilation. In this trial, cross-over to the alternate treatment was permitted if initial treatment failed. Investigators found no statistically significant differences in overall mortality (including survival after cross-over) between the two groups. In a secondary analysis, researchers showed that rescue treatment with HFJV, up to the time of cross-over, was associated with lower mortality. Researchers reported no differences in the incidence of chronic lung disease among survivors at 28 days of age, and they found no differences in intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis. Existing evidence does not support the use of rescue high-frequency jet ventilation compared with conventional mechanical ventilation for treatment of preterm infants with severe pulmonary problems. Additional research is needed.\n",
      "\n",
      "\n",
      "Idx 42\n",
      "We included five trials in this review, all were conducted in high-income countries. Three additional trials are ongoing. One trial compared fresh frozen plasma (FFP) transfusion with no transfusion given. One trial compared FFP or platelet transfusion or both with neither FFP nor platelet transfusion given. One trial compared FFP transfusion with administration of alternative pro-haemostatic agents (factors II, IX, and X followed by VII). One trial compared the use of different transfusion triggers using the international normalised ratio measurement. One trial compared the use of a thromboelastographic-guided transfusion trigger using standard laboratory measurements of coagulation. Four trials enrolled only adults, whereas the fifth trial did not specify participant age. Four trials included only minor procedures that could be performed by the bedside. Only one trial included some participants undergoing major surgical operations. Two trials included only participants in intensive care. Two trials included only participants with liver disease. Three trials did not recruit sufficient participants to meet their pre-calculated sample size. Overall, the quality of evidence was low to very low across different outcomes according to GRADE methodology, due to risk of bias, indirectness, and imprecision. One trial was stopped after recruiting two participants, therefore this review's findings are based on the remaining four trials (234 participants). When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in 30-day mortality (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.13 to 1.10; very low-quality evidence). We are very uncertain whether there was a difference in major bleeding within 24 hours (1 trial comparing FFP transfusion vs no transfusion, 76 participants; RR 0.33, 95% CI 0.01 to 7.93; very low-quality evidence; 1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; RR 1.59, 95% CI 0.28 to 8.93; very low-quality evidence). We are very uncertain whether there was a difference in the number of blood product transfusions per person (1 trial, 76 participants; study authors reported no difference; very low-quality evidence) or in the number of people requiring transfusion (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; study authors reported no blood transfusion given; very low-quality evidence) or in the risk of transfusion-related adverse events (acute lung injury) (1 trial, 76 participants; study authors reported no difference; very low-quality evidence). When plasma transfusion was compared with other pro-haemostatic agents, we are very uncertain whether there was a difference in major bleeding (1 trial; 21 participants; no events; very low-quality evidence) or in transfusion-related adverse events (febrile or allergic reactions) (1 trial, 21 participants; RR 9.82, 95% CI 0.59 to 162.24; very low-quality evidence). When different triggers for FFP transfusion were compared, the number of people requiring transfusion may have been reduced (for overall blood products) when a thromboelastographic-guided transfusion trigger was compared with standard laboratory tests (1 trial, 60 participants; RR 0.18, 95% CI 0.08 to 0.39; low-quality evidence). We are very uncertain whether there was a difference in major bleeding (1 trial, 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence) or in transfusion-related adverse events (allergic reactions) (1 trial; 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence). Only one trial reported 30-day mortality. No trials reported procedure-related harmful events (excluding bleeding) or quality of life. Review findings show uncertainty for the utility and safety of prophylactic FFP use. This is due to predominantly very low-quality evidence that is available for its use over a range of clinically important outcomes, together with lack of confidence in the wider applicability of study findings, given the paucity or absence of study data in settings such as major body cavity surgery, extensive soft tissue surgery, orthopaedic surgery, or neurosurgery. Therefore, from the limited RCT evidence, we can neither support nor oppose the use of prophylactic FFP in clinical practice.\n",
      "We included five trials which were all conducted in high-income countries. Our search is current up until 28 January 2019. One trial compared plasma transfusion with no transfusion given. Another trial compared plasma or platelet transfusion or both with neither plasma nor platelet transfusion given. One trial compared plasma transfusion with alternative products given to help blood clot. Another trial compared different blood tests to trigger a plasma transfusion, and still another trial compared different transfusion triggers using the same blood test. Four trials involved adult participants over 18 years old, and the fifth trial did not specify age of participants. In four trials, participants underwent bedside procedures. Only one trial involved some participants undergoing major surgical operations. Two trials included only participants in intensive care, and two trials included only participants with liver disease. One trial recruited only two participants. Therefore review results include the remaining four trials, incorporating 234 participants. Three further trials are ongoing. When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in major bleeding, number of blood transfusions per participant, or harmful effects from the transfusion (1 trial; very low-quality evidence). When plasma or platelet transfusion or both were compared with neither plasma nor platelet transfusion, we are very uncertain whether there was a difference in mortality within 30 days, or in the number of individuals requiring a transfusion (1 trial; very low-quality evidence). When plasma transfusion was compared with other haemostatic agents, we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion (1 trial; very low-quality evidence). When different triggers for plasma transfusion were compared (1 trial; 60 participants), we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion due to very low-quality evidence for these outcomes. The number of people requiring blood products may have been reduced overall, although this is based on low-quality evidence. No trials reported procedure-related harmful events or quality of life as an outcome. The overall quality of the evidence was predominantly very low over a range of clinically important outcomes due to combinations of issues within the studies, such as potential for bias, limited clinical settings, and imprecise estimates of intervention effects. We are very uncertain of the effectiveness and safety of the use of plasma in non-cardiac operations or invasive procedures due to very low-quality evidence. Furthermore, as trials do not cover a wide range of surgical contexts, our confidence in applying study results to the wider surgical setting is limited. Overall limited evidence for the utility of plasma transfused to people within this context is of insufficient quality to support or oppose its use.\n",
      "\n",
      "\n",
      "Idx 43\n",
      "We included 18 studies involving 1266 participants. We were not able to pool due to the heterogeneity of many of the studies. Our primary outcomes were 'Global improvement of nail psoriasis as rated by a clinician', 'Improvement of nail psoriasis scores (NAS, NAPSI)', 'Improvement of nail psoriasis in the participant's opinion'. Our secondary outcomes were 'Adverse effects (and serious adverse effects)'; 'Effects on quality of life'; and 'Improvement in nail features, pain score, nail thickness, thickness of subungual hyperkeratosis, number of affected nails, and nail growth'. We assessed short-term (3 to 6 months), medium-term (6 to 12 months), and long-term (> 12 months) treatments separately if possible. Two systemic biologic studies and three radiotherapy studies reported significant results for our first two primary outcomes. Infliximab 5 mg/kg showed 57.2% nail score improvement versus -4.1% for placebo (P < 0.001); golimumab 50 mg and 100 mg showed 33% and 54% improvement, respectively, versus 0% for placebo (P < 0.001), both after medium-term treatment. Infliximab and golimumab also showed significant results after short-term treatment. From the 3 radiotherapy studies, only the superficial radiotherapy (SRT) study showed 20% versus 0% nail score improvement (P = 0.03) after short-term treatment. Studies with ciclosporin, methotrexate, and ustekinumab were not significantly better than their respective comparators: etretinate, ciclosporin, and placebo. Nor were studies with topical interventions (5-fluorouracil 1% in Belanyx® lotion, tazarotene 0.1% cream, calcipotriol 50 ug/g, calcipotriol 0.005%) better than their respective comparators: Belanyx® lotion, clobetasol propionate, betamethasone dipropionate with salicylic acid, or betamethasone dipropionate. Of our secondary outcomes, not all included studies reported adverse events; those that did only reported mild adverse effects, and there were more in studies with systemic interventions. Only one study reported the effect on quality of life, and two studies reported nail improvement only per feature. Infliximab, golimumab, SRT, grenz rays, and electron beam caused significant nail improvement compared to the comparative treatment. Although the quality of trials was generally poor, this review may have some implications for clinical practice. Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is prescribed these systemic treatments because of cutaneous psoriasis or psoriatic arthritis or the nail psoriasis is severe, refractory to other treatments, or has a major impact on the person's quality of life. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work. Future trials need to be rigorous in design, with adequate reporting. Trials should correctly describe the participants' characteristics and diagnostic features, use standard validated nail scores and participant-reported outcomes, be long enough to report efficacy and safety, and include details of effects on nail features.\n",
      "Psoriasis is a common chronic skin disease with a prevalence in 2% to 3% of the population, according to European studies. Involvement of the nails occurs in about 50%. Nail psoriasis is difficult to treat, but may respond to some treatments. We aimed to review the efficacy and safety of the treatments used for nail psoriasis. We included 18 randomised controlled clinical trials (RCTs), which involved 1266 participants and were mostly based on a single study per treatment. Ten studies assessed topical treatments, i.e. applied to the surface of the skin (clobetasol, ciclosporin in maize oil, hyaluronic acid with chondroitin sulphates, 5-fluorouracil, a combination of dithranol with salicylic and UVB, tazarotene, and calcipotriol); 5 studies assessed systemic treatments, i.e. taken orally (golimumab, infliximab, ustekinumab, ciclosporin, and methotrexate); and 3 studies assessed radiotherapy (electron beam, grenz ray, and superficial radiotherapy). With regard to other treatments that are used for nail psoriasis, no RCTs had been carried out. It was not possible to pool and compare the results because the studies were all so different. In 5 studies, we found significant improvement of nail psoriasis compared to placebo: with infliximab (5 mg/kg), golimumab (50 mg and 100 mg), superficial radiotherapy, electron beam, and grenz rays. Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is a candidate for these systemic treatments because of skin psoriasis or psoriatic arthritis. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work. Topical treatment options could be beneficial and need to be further investigated. Clinical trials on nail psoriasis need to be rigorous in design, with clear reporting to enable readers to better interpret the results. Trials should accurately describe the participants' characteristics and diagnostic features of nail psoriasis; use standard validated nail scores and patient-reported outcomes; be long enough to report efficacy and safety; and include more details of effects on nail features.\n",
      "\n",
      "\n",
      "Idx 44\n",
      "Four studies with a total of 233 participants, comparing BTXA with placebo, met the inclusion criteria. In one study with 145 participants, significant improvement rates of pain intensity scores and duration of daily pain were demonstrated when comparing BTXA with placebo. The three other studies showed that there was no statistically significant difference between BTXA and placebo in pain intensity. Since the first publication of this review, no new studies were found. There is inconclusive evidence to support the use of botulinum toxin in the treatment of MPS based on data from four studies with a total of 233 participants, which we considered were of sufficient quality to be included in this review. Meta-analyses were not possible due to the heterogeneity between studies. We suggest that in future studies the same methodology to assess pain, a standardised dose of treatment, follow-up of at least four months (to observe the maximum and minimum curve of the drug effect) and appropriate data presentation should be used. More high-quality RCTs of botulinum toxin for treating MPS need to be conducted before firm conclusions on its effectiveness and safety can be drawn.\n",
      "The purpose of this review was to assess how effective botulinum toxin is at reducing pain in patients with MPS. We identified four studies, with 233 participants, comparing botulinum toxin A with placebo (control group). There was inconclusive evidence to support the use of botulinum toxin in the treatment of MPS. More high-quality randomised controlled trials of botulinum toxin for treating MPS need to be conducted before firm conclusions on its effectiveness and safety can be drawn.\n",
      "\n",
      "\n",
      "Idx 45\n",
      "We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of −0.43 (95% confidence interval (CI) −0.38 to −0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at −0.42 (95% CI −0.35 to −0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was −0.46 (95% CI −0.39 to −0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue. Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.\n",
      "We searched for all research published up to 1 April 2014, finding 32 relevant studies. There were 19 studies on five anti-TNF biologics (adalimumab, certolizumab, etanercept, golimumab and infliximab) and 12 studies on five non-anti-TNF biologics (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). Altogether 9,946 participants received biologics and 4,682 participants received standard therapy. All but two of the studies were randomised placebo-controlled trials, the gold standard in terms of study quality. We compared the effects of biologics versus placebo. In some studies, participants may have been taking standard therapy for rheumatoid arthritis at the start of the trial. In these studies, investigators added either biologics or placebo treatment to standard therapy. Overall, treatment by biologics led to small to moderate reductions (9 units reduction on a 0-52 scale) in patient-reported fatigue compared with 3 units in participants treated by placebo. It is unclear whether this improvement is due to a reduction in overall disease activity, a direct effect of the biologics or some other mechanism. There may have been some potential bias in the way investigators analysed data, and some studies did not include all randomised individuals, so we judged the quality of the evidence to be only moderate rather than high.\n",
      "\n",
      "\n",
      "Idx 46\n",
      "The search resulted in 2693 articles that we screened on title and abstract for eligibility.Thirteen studies were selected for full text assessment. We included three randomised trials involving 1150 women. Two trials compared the administration of prostaglandins in the morning versus the evening in women with an unfavourable cervix, and one trial compared induction of labour in the morning versus the evening in women with a favourable cervix and/or ruptured membranes with intravenous oxytocin. Because of the different mechanism, we have reported results for these two comparisons separately. In the two trials comparing prostaglandins in the morning versus the evening there were few clinically significant differences between study groups for maternal or neonatal outcomes. One study reported a statistically significant preference by women to start induction of labour with prostaglandins in the morning. In the trial examining induction of labour with intravenous oxytocin, the number of neonatal admissions was statistically significantly increased in the group of women that started induction in the morning. This finding was unexpected, and while the trial authors offered some possible explanations for this, it is important that any future trials examine neonatal outcomes. Taking into account women's preferences that favoured administration of prostaglandins in the morning, we conclude that caregivers should preferably consider administering prostaglandins in the morning. There is no strong evidence that induction of labour with intravenous oxytocin in the evening is more or less effective than induction in the morning. Consideration may be given to start induction of labour with oxytocin in the evening when indicated.\n",
      "In human and animal studies however, spontaneous onset of labour is proven to have a circadian rhythm with preference for start in the evening. Moreover, when spontaneous labour starts in the evening, total duration of labour shortens and less obstetric interventions are needed. Based on these observations one might assume, that starting induction of labour in harmony with the circadian rhythm of natural birth is more beneficial. This review found three studies that were of high quality with a total of 1150 women randomly allocated to induction in the morning or the evening. One trial used intravenous oxytocin in women who had a dilated cervix or rupture of membranes and two trials used prostaglandins to induce labour. Prostaglandins are hormones used when the cervix is not ripe, intravenous oxytocin is mostly needed afterwards to really get labour started. Therefore, these two different methods, prostaglandins and intravenous oxytocin, rely on a different mechanism and were assessed separately. This review found no differences in effect between starting induction in morning or evening on outcomes for mother or child. The risk of a vaginal birth using instruments, or risk of a caesarian section and use of epidural anaesthesia did not clearly differ between groups. One study reported that women had a preference to start induction of labour with prostaglandins in the morning, and more women in the evening admission group did not like the interruptions to sleep that were associated with the induction protocol. This review, with only three studies with two different comparisons, concludes that induction of labour in the evening is as effective and safe as induction in the morning. However, given the preference of most women, administration of prostaglandins should preferably be done in the morning.\n",
      "\n",
      "\n",
      "Idx 47\n",
      "We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real-world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low-quality evidence that showed no significant difference in 30-day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate-quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate-quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs. Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30-day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well-conducted, adequately-powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs.\n",
      "We found 14 studies involving 698 participants. Whilst all 14 studies compared broadly the analgesic efficacy of PVB and TEB in participants undergoing open thoracotomy, there were significant differences in the timing, method of insertion and medications used in PVB and TEB. This makes direct comparison difficult. Patient follow-up was limited to the immediate post-surgery period (up to five days post-surgery) with only two studies reporting long-term outcomes such as chronic pain. There are two studies awaiting classification. We found no difference between PVB and TEB in terms of death at 30 days and major complications. PVB appeared to be as effective as TEB in pain control post-surgery. TEB was associated with minor complications such as low blood pressure, nausea and vomiting, itching and urinary retention when compared to PVB. We did not find any difference in length of hospital stay between PVB and TEB. There was insufficient information to assess chronic pain and health costs. We found low-quality evidence for death at 30 days, with limited information provided by only two studies reporting this outcome. We only found low to very low-quality evidence for major complications due to lack of information, with only one study reporting these outcomes. We found moderate-quality evidence for acute pain control in the immediate postoperative period. We found moderate-quality evidence for minor complications.\n",
      "\n",
      "\n",
      "Idx 48\n",
      "We included eight trials in this review with a total of 1708 participants. Trials were conducted in India, Nepal and South Africa. Follow-up ranged from one day to six months, but most trials reported at six to eight weeks after surgery. Overall the trials were judged to be at risk of bias due to unclear reporting of masking and follow-up. No studies reported presenting visual acuity so data were collected on both best-corrected (BCVA) and uncorrected (UCVA) visual acuity. Most studies reported visual acuity of 6/18 or better (rather than 6/12 or better) so this was used as an indicator of good functional vision. Seven studies (1223 participants) reported BCVA of 6/18 or better at six to eight weeks (pooled risk ratio (RR) 0.99 95% confidence interval (CI) 0.98 to 1.01) indicating no difference between the MSICS and phacoemulsification groups. Three studies (767 participants) reported UCVA of 6/18 or better at six to eight weeks, with a pooled RR indicating a more favourable outcome with phacoemulsification (0.90, 95% CI 0.84 to 0.96). One trial (96 participants) reported UCVA at six months with a RR of 1.07 (95% CI 0.91 to 1.26). Regarding BCVA of less than 6/60: there were only 11/1223 events reported. The pooled Peto odds ratio was 2.48 indicating a more favourable outcome using phacoemulsification but with wide confidence intervals (0.74 to 8.28) which means that we are uncertain as to the true effect. The number of complications reported were also low for both techniques. Again this means the review is underpowered to detect a difference between the two techniques with respect to these complications. One study reported on cost which was more than four times higher using phacoemulsification than MSICS. On the basis of this review, removing cataract by phacoemulsification may result in better UCVA in the short term (up to three months after surgery) compared to MSICS, but similar BCVA. There is a lack of data on long-term visual outcome. The review is currently underpowered to detect differences for rarer outcomes, including poor visual outcome. In view of the lower cost of MSICS, this may be a favourable technique in the patient populations examined in these studies, where high volume surgery is a priority. Further studies are required with longer-term follow-up to better assess visual outcomes and complications which may develop over time such as posterior capsule opacification.\n",
      "We searched the literature in July 2013 and identified eight randomised controlled trials that compared these two techniques. These included a total of 1708 participants randomly allocated to MSICS or phacoemulsification. The studies were carried out in India, Nepal and South Africa. Not all studies reported the outcomes of visual acuity that we aimed to assess, making it difficult to draw definite conclusions. Better uncorrected visual acuity was seen in the short term with phacoemulsification; however, there were no differences in best-corrected visual acuity (i.e. after correction with spectacles). There appeared to be no significant difference regarding uncorrected visual acuity between the two techniques at six months in the one trial that reported at that time point. There was a lack of long-term data (one year or more after surgery). Very few participants were reported to have poor visual outcomes or complications (such as posterior capsule rupture) from the surgery. The cost of phacoemulsification was documented in one study only, and this was more than four times the cost of MSICS. In this setting, the two techniques appear to be comparable in terms of visual acuity outcomes and complications. However further studies with a longer follow-up period are needed to better assess these outcomes.\n",
      "\n",
      "\n",
      "Idx 49\n",
      "Of the 908 participants enrolled (three RCTs), 454 were allocated for drainage and 454 for no drainage. We found no new RCTs for this review update. Two trials reported the primary outcome measure of anastomotic dehiscence. There was no statistically significant difference in anastomotic dehiscence in participants treated with intra-abdominal drainage routinely compared to no treatment (risk ratio (RR) 1.40, 95% confidence intervals (CI) 0.45 to 4.40; I2 = 0%; 2 RCTs; 809 participants). There was no statistically significant difference in mortality (RR 0.77, 95% CI 0.41 to 1.45; I2 = 0%; 3 RCTs; 908 participants); surgical re-intervention (RR 1.11, 95% CI 0.67 to 1.82; I2 = 29%; 3 RCTs; 908 participants); radiological dehiscence (RR 0.85, 95% CI 0.39 to 1.83; I2 = 0%; 2 RCTs; 809 participants) and wound infection (RR 0.82, 95% CI 0.45 to 1.51; I2 = 0%; 3 RCTs; 908 participants) in participants treated with routine prophylactic drainage compared to no treatment undergoing elective colorectal surgery. The quality of evidence was low according to GRADE method assessment. There was insufficient evidence for the use of prophylactic drains after elective colorectal anastomoses. The conclusions of this review were limited due to the nature of the available clinical data; The three included RCTs performed different interventions with relatively small sample sizes of eligible participants.\n",
      "We included three clinical trials involving 908 participants. The trials were conducted in Germany and France. All trials compared routine anastomotic drainage versus no anastomotic drainage after elective colorectal surgery. The evidence was current to February 2015. This review showed no apparent difference in anastomotic leak, death, radiological (x-ray) evidence of anastomotic leak, wound infection or need for re-operation. We found insufficient evidence to support the use of routine prophylactic drains after elective colorectal anastomosis. We based our conclusion on limited evidence with relatively small numbers of participants; this means that it is difficult to detect differences between treatment groups that may be present. The quality of the evidence was low, making it impossible to draw firm conclusions about the use of routine prophylactic drains after elective colorectal anastomosis. Additional studies are needed to strengthen the conclusion drawn by this systematic review and to provide further analysis using modern colorectal surgery. We found no new evidence since the previous version of our systematic review of 2004.\n",
      "\n",
      "\n",
      "Idx 50\n",
      "The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks). It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I2 = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I2 = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I2 = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I2 = 0%, low quality evidence from 3 trials, 102 participants). PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.\n",
      "We included 10 randomised clinical trials, with a total of 442 participants (mean age 61 years and 42% women). Four included studies recruited people with a range of chronic wounds; three studies enrolled people with venous leg ulcers; and the other three studies included people with diabetes who had foot ulcers. The median length of treatment was 12 weeks. All but three trials reported the sources of funding. Four of the studies received financial support from companies manufacturing PRP devices. The results were non-conclusive as to whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment. Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care, but it is unclear if autologous PRP has an effect on other types of chronic wound. Three studies reported wound complications such as infection or dermatitis, but results showed no difference in the risk of adverse events in people treated with PRP or standard care. These findings are based on low quality evidence due to the small number of studies and patients included, and their poor methodological quality. This Plain Language Summary is up to date as of 16 June 2015.\n",
      "\n",
      "\n",
      "Idx 51\n",
      "Two cluster-randomised control trials were included: one randomised at hospital level (23 hospitals in Australia) and one at ward level (16 wards in the UK). The primary outcome in the Australian trial (a composite score comprising incidence of unexpected cardiac arrests, unexpected deaths and unplanned ICU admissions) showed no statistical significant difference between control and medical emergency team (MET) hospitals (adjusted P value 0.640; adjusted odds ratio (OR) 0.98; 95% confidence interval (CI) 0.83 to 1.16). The UK-based trial found that outreach reduced in-hospital mortality (adjusted OR 0.52; 95% CI 0.32 to 0.85) compared with the control group. The evidence from this review highlights the diversity and poor methodological quality of most studies investigating outreach. The results of the two included studies showed either no evidence of the effectiveness of outreach or a reduction in overall mortality in patients receiving outreach. The lack of evidence on outreach requires further multi-site RCT's to determine potential effectiveness.\n",
      "This summary of a Cochrane review presents what we know from research about the effect of outreach services for patients on general hospital wards. The review found two studies which were of good quality. One study compared 12 hospitals with outreach services to 11 that did not. Another study compared 16 wards with outreach to general wards without outreach. One of the studies showed that outreach reduced the number of hospital deaths, while the other study found no differences between hospitals with outreach and those with no outreach. It is not clear whether outreach reduces hospital deaths or ICU admissions. High quality research is needed to determine the effect of outreach services.\n",
      "\n",
      "\n",
      "Idx 52\n",
      "We included six new studies (624 participants) for this update, which now includes a total of 23 trials that randomised a total of 2890 participants undergoing cardiac rehabilitation. Participants had an acute myocardial infarction, revascularisation or heart failure. A number of studies provided insufficient detail to enable assessment of potential risk of bias, in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported. No evidence of a difference was seen between home- and centre-based cardiac rehabilitation in clinical primary outcomes up to 12 months of follow up: total mortality (relative risk (RR) = 1.19, 95% CI 0.65 to 2.16; participants = 1505; studies = 11/comparisons = 13; very low quality evidence), exercise capacity (standardised mean difference (SMD) = -0.13, 95% CI -0.28 to 0.02; participants = 2255; studies = 22/comparisons = 26; low quality evidence), or health-related quality of life up to 24 months (not estimable). Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate quality evidence). However, there was evidence of marginally higher levels of programme completion (RR 1.04, 95% CI 1.00 to 1.08; participants = 2615; studies = 22/comparisons = 26; low quality evidence) by home-based participants. This update supports previous conclusions that home- and centre-based forms of cardiac rehabilitation seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction or revascularisation, or with heart failure. This finding supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme may reflect local availability and consider the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in the included short-term trials can be confirmed in the longer term and need to consider adequately powered non-inferiority or equivalence study designs.\n",
      "We searched for randomised controlled trials (trials that randomly allocate participants to one of two or more treatment groups) looking at the effectiveness of home-based versus supervised centre-based cardiac rehabilitation programmes, in adults with heart disease. We included 23 trials (2890 participants). Most trials were relatively small (median 104 participants, range: 20 to 525). The average age of trial participants ranged from 51.6 to 69 years. Women accounted for only 19% of recruited participants; four trials did not include women. The mix of people recruited to the trials varied; 10 studies included a mixed population of people with coronary heart disease, five studies included people who had had a heart attack, and four studies each recruited people following revascularisation or who had heart failure. Sixteen studies reported sources of funding; seven did not. No study reported funding from an agency with commercial interest in the results. We found that home- and centre-based cardiac rehabilitation programmes are similar in benefits measured in terms of numbers of deaths, exercise capacity and health-related quality of life. Further data are needed to confirm if these short-term effects of home- and centre-based cardiac rehabilitation can be sustained over time. Poor reporting made it difficult to assess methodological quality of the included studies and their risk of bias. Evidence quality ranged from very low (total mortality), to moderate (exercise capacity over 12 months and health-related quality of life). The main reasons for the low assessment of quality was poor reporting in the included studies.\n",
      "\n",
      "\n",
      "Idx 53\n",
      "We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged as being at least at moderate risk of bias. The strength of the evidence was weak for the majority of outcomes, which was mostly because of the small numbers of evaluable patients, varying definitions, as well as unclear measurements of the trials' outcomes and uncertain influences of supportive treatments on them. In most trials, the chemotherapy regimens had a risk of FN that was below the threshold at which current guidelines recommend routine primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity which can be explained by possible differential effects of G-CSFs and GM-CSFs and different definitions of FN. A significant reduction in early mortality was observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 patients; wherein 19 of these 23 events occurred in one study and 17 events were attributed to progression of the disease by the study authors. For infection-related mortality, there were no significant differences between CSF and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the scheduled dose of chemotherapy did not differ between CSF-treated and control groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number needed to treat for an additional harmful outcome (NNTH) 3) and injection-site reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of beneﬁt in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.\n",
      "This review included eight trials in which 2156 patients with breast cancer had randomly received CSFs or placebo or no treatment during chemotherapy. These trials were carried out between 1995 and 2008. Prophylactic treatment with CSFs significantly reduced the risk of developing FN by 73%. The estimated number of patients needed to be treated with CSFs in order to prevent one event of FN was 12. Although a significant decrease in mortality of all causes during chemotherapy and CSF therapy was noted, there was no reduction in infection-related mortality. There was no significant effect observed that planned chemotherapy schedules could be better maintained if CSFs were administered or that the number of patients with neutropenia decreased with CSFs. Notably, CSFs significantly reduced the need for hospital care yet frequently caused short-term adverse effects like bone pain and injection-site reactions. There were several limitations in this analysis: only a few trials could be included, the number of patients was low in many of these trials, and disease stages and chemotherapy treatments varied considerably. Moreover, the trial authors defined their outcomes differently, making comparisons across studies difficult. Information on the primary and secondary outcomes could not be obtained from all trials and the overall reporting quality was low. Many studies were dated and hence the administration of CSFs did not comply with current recommendations. Overall, CSFs have shown moderate evidence of beneﬁt in the prevention of FN in patients with breast cancer receiving chemotherapy. The evidence that the administration of CSFs could reduce early mortality of all causes was weak and substantiates the need of further studies. There was no reduction in risk of infection-related mortality with CSF treatment.\n",
      "\n",
      "\n",
      "Idx 54\n",
      "We identified one trial comparing early versus delayed laparoscopic cholecystectomy for people with mild acute pancreatitis. Fifty participants with mild acute gallstone pancreatitis were randomised either to early laparoscopic cholecystectomy (within 48 hours of admission irrespective of whether the abdominal symptoms were resolved or the laboratory values had returned to normal) (n = 25), or to delayed laparoscopic cholecystectomy (surgery after resolution of abdominal pain and after the laboratory values had returned to normal) (n = 25). This trial is at high risk of bias. There was no short-term mortality in either group. There was no significant difference between the groups in the proportion of participants who developed serious adverse events (RR 0.33; 95% CI 0.01 to 7.81). Health-related quality of life was not reported in this trial. There were no conversions to open cholecystectomy in either group. The total hospital stay was significantly shorter in the early laparoscopic cholecystectomy group than in the delayed laparoscopic cholecystectomy group (MD -2.30 days; 95% CI -4.40 to -0.20). This trial reported neither the number of work-days lost nor the costs. We did not identify any trials comparing early versus delayed laparoscopic cholecystectomy after severe acute pancreatitis. There is no evidence of increased risk of complications after early laparoscopic cholecystectomy. Early laparoscopic cholecystectomy may shorten the total hospital stay in people with mild acute pancreatitis. If appropriate facilities and expertise are available, early laparoscopic cholecystectomy appears preferable to delayed laparoscopic cholecystectomy in those with mild acute pancreatitis. There is currently no evidence to support or refute early laparoscopic cholecystectomy for people with severe acute pancreatitis. Further randomised controlled trials at low risk of bias are necessary in people with mild acute pancreatitis and severe acute pancreatitis.\n",
      "We identified one trial comparing early versus delayed laparoscopic cholecystectomy for people with mild acute pancreatitis. Out of the 50 participants included in this trial, 25 underwent early laparoscopic cholecystectomy while the remaining 25 underwent delayed laparoscopic cholecystectomy. All 50 participants were alive at the end of the trial. There was no significant difference between the two groups in the proportion of participants who developed complications. Health-related quality of life was not reported in this trial. There were no conversions to open cholecystectomy in either group. The total hospital stay was shorter by approximately two days in the early laparoscopic cholecystectomy group than in the delayed laparoscopic cholecystectomy group. The trial did not report the number of work-days lost or the costs. We did not identify any trials comparing early versus delayed laparoscopic cholecystectomy after severe acute pancreatitis. Based on the observations in the one trial included in this review, there appears to be no evidence of increased risk of complications after early laparoscopic cholecystectomy. Early laparoscopic cholecystectomy may shorten the total hospital stay in people with mild acute pancreatitis. If appropriate facilities and expertise are available, early laparoscopic cholecystectomy appears preferable to delayed laparoscopic cholecystectomy in people with mild acute pancreatitis. There is currently no evidence to support or refute early laparoscopic cholecystectomy for people with severe acute pancreatitis. Further well-designed randomised controlled trials are necessary in people with mild acute pancreatitis and severe acute pancreatitis. The one trial identified is at high risk of bias, i.e. there was potential to arrive at wrong conclusions because of the way that the study was designed and conducted.\n",
      "\n",
      "\n",
      "Idx 55\n",
      "We included 24 studies that involved a total of 1787 participants. Studies reported on various types of acupuncture and related interventions including manual acupuncture and acupressure, ear acupressure, transcutaneous electrical acupuncture point stimulation, far-infrared radiation on acupuncture points and indirect moxibustion. CKD stages included pre-dialysis stage 3 or 4 and end-stage kidney disease on either haemodialysis or peritoneal dialysis. None of the included studies assessed pain outcomes, nor formally addressed occurrence of serious adverse events, although three studies reported three participant deaths and three hospitalisations as reasons for attrition. Three studies reported minor acupuncture-related harms; the remainder did not report if those events occurred. All studies were assessed at high or unclear risk of bias in terms of allocation concealment. Seventeen studies reported outcomes measured for only two months. There was very low quality of evidence that compared with routine care, manual acupressure reduced scores of the Beck Depression Inventory score (scale from 0 to 63) (3 studies, 128 participants: MD -4.29, 95% CI -7.48 to -1.11, I2 = 0%), the revised Piper Fatigue Scale (scale from 0 to 10) (3 studies, 128 participants: MD -1.19, 95% CI -1.77 to -0.60, I2 = 0%), and the Pittsburgh Sleep Quality Index (scale from 0 to 21) (4 studies, 180 participants: MD -2.46, 95% CI -4.23 to -0.69, I2 = 50%). We were unable to perform further meta-analyses because of the paucity of data and problems with clinical heterogeneity, such as different interventions, comparisons and timing of outcome measurements. There was very low quality of evidence of the short-term effects of manual acupressure as an adjuvant intervention for fatigue, depression, sleep disturbance and uraemic pruritus in patients undergoing regular haemodialysis. The paucity of evidence indicates that there is little evidence of the effects of other types of acupuncture for other outcomes, including pain, in patients with other stages of CKD. Overall high or unclear risk of bias distorts the validity of the reported benefit of acupuncture and makes the estimated effects uncertain. The incomplete reporting of acupuncture-related harm does not permit us to assess the safety of acupuncture and related interventions. Future studies should investigate the effects and safety of acupuncture for pain and other common symptoms in patients with CKD and those undergoing dialysis.\n",
      "We searched the literature up to January 2016 and analysed 24 studies that involved 1787 participants. Of these, only seven studies provided data that could be combined for analysis. The studies reported that manual acupressure improved fatigue, depression and sleep disturbance when used as an adjunct to routine care for patients undergoing maintenance haemodialysis 4 weeks from baseline. No study assessed pain and most did not report whether adverse events of acupuncture occurred. Overall, we found very low quality evidence about the effectiveness of acupuncture for symptoms of CKD. Manual acupressure combined with routine care may provide short-term symptom relief from depressive mood, fatigue and sleep disturbance in patients undergoing haemodialysis. Findings from this review cannot support the benefits of other acupuncture techniques for patients with CKD because there were too few reliable studies. Pain is a common condition in patients with CKD. Thus, the potential role of acupuncture for pain control in patients with CKD deserves further research. Clinicians should carefully monitor the safety of acupuncture in patients with CKD unless sound evidence supports the safety of these interventions for CKD patients. All studies were assessed at high or unclear risk of bias, especially in terms of selection of participants and selective outcome reporting, which made the validity of their results doubtful.\n",
      "\n",
      "\n",
      "Idx 56\n",
      "The search identified 16 eligible studies, in which only adults with cirrhosis were included. In one study, people with portal thrombosis were also included. We classified most of the studies at high risk of bias for the 'Participants selection' and the 'Flow and timing' domains. One study assessed the accuracy of capsule endoscopy for the diagnosis of large (high-risk) oesophageal varices. In the remaining15 studies that assessed the accuracy of capsule endoscopy for the diagnosis of oesophageal varices of any size in people with cirrhosis, 936 participants were included; the pooled estimate of sensitivity was 84.8% (95% confidence interval (CI) 77.3% to 90.2%) and of specificity 84.3% (95% CI 73.1% to 91.4%). Eight of these studies included people with suspected varices or people with already diagnosed or even treated varices, or both, introducing a selection bias. Seven studies including only people with suspected but unknown varices were at low risk of bias; the pooled estimate of sensitivity was 79.7% (95% CI 73.1% to 85.0%) and of specificity 86.1% (95% CI 64.5% to 95.5%). Six studies assessed the diagnostic accuracy of capsule endoscopy for the diagnosis of large oesophageal varices, associated with a higher risk of bleeding; the pooled sensitivity was 73.7% (95% CI 52.4% to 87.7%) and of specificity 90.5% (95% CI 84.1% to 94.4%). Two studies also evaluated the presence of red marks, which are another marker of high risk of bleeding; the estimates of sensitivity and specificity varied widely. Two studies obtained similar results with the use of a modified device as index test (string capsule). Due to the absence of data, we could not perform all planned subgroup analyses. Interobserver agreement in the interpretation of capsule endoscopy results and any adverse event attributable to capsule endoscopy were poorly assessed and reported. Only four studies evaluated the interobserver agreement in the interpretation of capsule endoscopy results: the concordance was moderate. The participants' preferences for capsule endoscopy or oesophago-gastro-duodenoscopy were reported differently but seemed in favour of capsule endoscopy in nine of 10 studies. In 10 studies, participants reported some minor discomfort on swallowing the capsule. Only one study identified other significant adverse events, including impaction of the capsule due to previously unidentified oesophageal strictures in two participants. No adverse events were reported as a consequence of the reference standard. We cannot support the use of capsule endoscopy as a triage test in adults with cirrhosis, administered before oesophago-gastro-duodenoscopy, despite the low incidence of adverse events and participant reports of being better tolerated. Thus, we cannot conclude that oesophago-gastro-duodenoscopy can be replaced by capsule endoscopy for the detection of oesophageal varices in adults with cirrhosis. We found no data assessing capsule endoscopy in children and in people with portal thrombosis.\n",
      "We searched scientific databases for clinical studies comparing OGD to capsule endoscopy and reporting the size and appearance of varices in children or adults with chronic liver disease or portal vein thrombosis (narrowing of the portal vein). The evidence is current to October 2013. We found 16 studies assessing the ability of capsule endoscopy to diagnose the presence of varices and grade the risk of bleeding and comparing it with OGD in adults with cirrhosis. Capsule endoscopy, even if more acceptable to participants, cannot replace OGD for the detection of oesophageal varices as about 15% are left undetected and 15% are not confirmed by endoscopy. Even the accuracy in detecting large varices or red marks on varices was very lower than endoscopy. Hence, in conclusion, capsule endoscopy is not sufficiently accurate to replace OGD for the detection of oesophageal varices in cirrhotic participants. In nine of the sixteen studies there were problems concerning participant selection and incompleteness of reported data which impair accuracy estimates and the transferability of the results.\n",
      "\n",
      "\n",
      "Idx 57\n",
      "We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer-term follow-up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes.\n",
      "We identified six randomised controlled trials involving a total of 794 women and their babies for this review. The trials were of moderate risk of bias overall. The trials did not demonstrate differences between calcium channel blocker maintenance therapy and placebo or no treatment in the prevention of preterm birth or perinatal death (fetal or neonatal deaths). None of the trials included any follow-up of the infants to assess longer-term development. Calcium channel blocker maintenance therapy (with a drug called nifedipine) was more likely than placebo or no treatment to prolong pregnancy, however the infants of these mothers were more likely to have a longer hospital stay. Based on the current studies, we found no convincing evidence that calcium channel blocker maintenance therapy prevents preterm birth for women after threatened preterm labour, or that it improves outcomes for babies.\n",
      "\n",
      "\n",
      "Idx 58\n",
      "We identified eight studies with a total of 204 participants and a mean sample size of 25. All trials were single-centre trials, and participants seen on an outpatient basis. Seven studies compared medication and placebo (n = 184); one study compared medication and another active agent (n = 13). Duration of the studies was six to twelve weeks. Meta-analysis was not undertaken because of the methodological heterogeneity of the trials. The studies did not employ intention-to-treat analyses and were at a high risk of attrition bias. Adverse events were not well-documented in the studies. None of the three studies of selective serotonin reuptake inhibitors (SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment. No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes.\n",
      "This systematic review of randomised controlled trials (RCTs) set out to review the evidence for medication in treating TTM. The findings are based on eight studies (which included a total of 204 people). Not enough evidence was found to conclude definitively that any particular medication is effective in the treatment of TTM. Furthermore, side effects related to medications were not well-documented in the majority of the studies. Because of differences in the way the included studies were carried out, we were unable to combine their results to draw more conclusive evidence. However, an early trial found some evidence for the efficacy of clomipramine, and two recent trials reported statistically significant treatment outcomes with olanzapine and N-acetylcysteine. More research is needed to find an optimal treatment for TTM.\n",
      "\n",
      "\n",
      "Idx 59\n",
      "Nine studies (1265 participants) met the inclusion criteria of the review. Two studies were conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Lung function was not significantly different between extrafine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in FEV1 predicted: -2.18% (95% CI -4.62 to 0.26; three studies, 334 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and extrafine HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event. There was no significant difference between FP and extrafine HFA-BDP on FEV1 or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. Only two small paediatric studies were included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.\n",
      "The review of studies found that there was a limited amount of evidence to show that the newer extra-fine form of BDP was similar to FP at the same dose. More research should be done in children and in people with more severe asthma to help answer the question of what the relative effects of these two steroids are. Some people may not be particularly good at using certain inhaler types and the findings of the review may only really apply to people who are competent in using metered-dose inhalers (MDIs). Studies should consider introducing spacers where people find these easier to use.\n",
      "\n",
      "\n",
      "Idx 60\n",
      "We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification. All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials. Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications. Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure. Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93). Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.\n",
      "We included 17 studies evaluating systemic corticosteroid therapy (given intravenously or by tablets) for people with pneumonia (2264 participants; 1954 adults and 310 children). We included 12 new studies in this update and excluded one previously included study. All included studies evaluated people who had acquired pneumonia in the community (community-acquired pneumonia (CAP)) being treated in the hospital; no studies assessed people who had developed pneumonia while in hospital or who were on breathing machines (mechanically ventilated). Eight trials did not report funding sources; seven were funded by academic sponsors; one was funded by a pharmaceutical company; and one reported receiving no funding. Corticosteroids reduced deaths in adults with severe CAP, but not in people with non-severe CAP. Eighteen adults with severe CAP need to be treated with corticosteroids to prevent one death. People with CAP treated with corticosteroids had lower clinical failure rates (death, worsening of imaging studies, or no clinical improvement), shorter time to cure, a shorter hospital stay, and fewer complications. We found good-quality evidence that corticosteroids reduced clinical failure rates in children with pneumonia, but the data were based on a small number of children with different types of pneumonia. People treated with corticosteroids had higher blood glucose levels (hyperglycaemia) than those not treated with corticosteroids. Corticosteroid treatment was not associated with increased rates of other serious adverse events. Corticosteroids were beneficial for adults with severe CAP. People with non-severe CAP may also benefit from corticosteroid therapy, but with no survival advantage. We downgraded the quality of the evidence due to issues with study design, unclear results, or results that were not similar across studies. For the outcomes of death and clinical failure in adults, we graded the quality of the evidence as moderate. For the outcomes of clinical failure in people with severe CAP, non-severe CAP, and in children, we graded the quality of the evidence as high.\n",
      "\n",
      "\n",
      "Idx 61\n",
      "Twelve randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended or continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended or continuous cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group. The studies that reported menstrual symptoms found that the extended or continuous group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven out of the twelve studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles over time. Endometrial lining assessments by ultrasound and/or endometrial biopsy were done in some participants and were all normal after cyclic or extended CHC use. The 2014 update yielded four additional trials but unchanged conclusions. Evidence from existing randomized control trials comparing continuous or extended-cycle CHCs (greater than 28 days of active combined hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormone and 4 days of placebo) is of good quality. However, the variations in type of hormones and time length for extended-cycle dosing make a formal meta-analysis impossible. Future studies should choose a previously described type of CHC and dosing regimen. More attention needs to be directed towards participant satisfaction, continuation, and menstruation-associated symptoms.\n",
      "Delaying or eliminating the break in hormone use has become a popular way for women to avoid monthly bleeding, so we performed this review to compare these newer regimens to traditional CHC dosing regimens. We searched for all randomized controlled trials on this question in any language; we found twelve that met our criteria. The continuous or extended-cycle and traditional regimens appeared similar, as judged by bleeding, discontinuation rates, and reported satisfaction. The studies were too small to address efficacy, rare adverse events, and safety. Extended-cycle (for more than 28 days) or continuous dosing appears to be a reasonable approach to CHC use.\n",
      "\n",
      "\n",
      "Idx 62\n",
      "A total of 798 studies were identified following the initial search. No published or unpublished randomised controlled trials comparing primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who were treated with chemo/radiotherapy were identified. Seven non-randomised studies, potentially eligible for inclusion, were identified: 2 case-matched studies, 2 CCTs and 3 retrospective cohort studies. Overall, these trials included 1.086 patients (722 patients treated with primary tumour resection, and 364 patients managed first with chemotherapy and/or radiotherapy). Resection of the primary tumour in asymptomatic patients with unresectable stage IV colorectal cancer who are managed with chemo/radiotherapy is not associated with a consistent improvement in overall survival. In addition, resection does not significantly reduce the risk of complications from the primary tumour (i.e.  obstruction, perforation or bleeding). Yet there is enough doubt with regard to the published literature to justify further clinical trials in this area. The results from an ongoing high quality randomised controlled trial will help to answer this question.\n",
      "Some studies have suggested that resecting the primary cancer can prolong survival and prevent complication arising from the cancer, such as obstruction or bleeding. This review addresses the question of whether surgically removing the primary cancer is beneficial to patients with advanced and unresectable colorectal cancer. No randomised controlled trials were identified.\n",
      "\n",
      "\n",
      "Idx 63\n",
      "A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi2 40.51, df = 6, P < 0.00001; I2 = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review. The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens.\n",
      "Clinical trials have come to different conclusions about the best approach. We conducted a systematic review and meta-analysis to synthesize available clinical research studies that have examined outcome according to donor vs. no donor status, or genetic randomization. This is a method of analysis for assessing the effect of transplantation in this disease condition. Our analysis supports matched sibling donor allogeneic hematopoeitic cell transplantation as the approach which offers the best long-term outcomes, specifically providing optimal survival and reduced risk for ALL relapse.\n",
      "\n",
      "\n",
      "Idx 64\n",
      "Thirty eight randomised controlled comparisons (made within 22 trials) were identified. Most were based on 'healthy' adult participants who were not considered to be at increased risk of regurgitation or aspiration during anaesthesia. Few trials reported the incidence of aspiration/regurgitation or related morbidity but relied on indirect measures of patient safety i.e. intra-operative gastric volume and pH. There was no evidence that the volume or pH of participants' gastric contents differed significantly depending on whether the groups were permitted a shortened preoperative fluid fast or continued a standard fast. Fluids evaluated included water, coffee, fruit juice, clear fluids and other drinks (e.g. isotonic drink, carbohydrate drink). Participants given a drink of water preoperatively were found to have a significantly lower volume of gastric contents than the groups that followed a standard fasting regimen. This difference was modest and clinically insignificant. There was no indication that the volume of fluid permitted during the preoperative period (i.e. low or high) resulted in a difference in outcomes from those participants that followed a standard fast. Few trials specifically investigated the preoperative fasting regimen for patient populations considered to be at increased risk during anaesthesia of regurgitation/aspiration and related morbidity. There was no evidence to suggest a shortened fluid fast results in an increased risk of aspiration, regurgitation or related morbidity compared with the standard 'nil by mouth from midnight' fasting policy. Permitting patients to drink water preoperatively resulted in significantly lower gastric volumes. Clinicians should be encouraged to appraise this evidence for themselves and when necessary adjust any remaining standard fasting policies (nil-by-mouth from midnight) for patients that are not considered 'at-risk' during anaesthesia.\n",
      "However, the review of trials found that drinking clear fluids up to a few hours before surgery did not increase the risk of regurgitation during or after surgery. Some people are considered more likely to regurgitate under anaesthetic, including those who are pregnant, elderly, obese or have stomach disorders. More research is needed to determine whether these people can also safely drink up to a few hours before surgery.\n",
      "\n",
      "\n",
      "Idx 65\n",
      "We included two RCTs (involving 154 women) with a low risk of bias. It was not possible to pool the available studies. The two studies do not consistently report outcomes defined in the review. However, no significant differences were observed between the two groups (surgical versus non-surgical repair) in incidence of pain and wound complications, self-evaluated measures of pain at hospital discharge and postpartum and re-initiation of sexual activity. Differences in the use of analgesia varied between the studies, being high in the sutured group in one study. The other trial showed differences in wound closure and poor wound approximation in the non-suturing group, but noted incidentally also that more women were breastfeeding in this group. There is limited evidence available from RCTs to guide the choice between surgical or non-surgical repair of first- or second-degree perineal tears sustained during childbirth. Two studies find no difference between the two types of management with regard to clinical outcomes up to eight weeks postpartum. Therefore, at present there is insufficient evidence to suggest that one method is superior to the other with regard to healing and recovery in the early or late postnatal periods. Until further evidence becomes available, clinicians' decisions whether to suture or not can be based on their clinical judgement and the women's preference after informing them about the lack of long-term outcomes and the possible chance of a slower wound healing process, but possible better overall feeling of well being if left un-sutured.\n",
      "Our review included two randomised controlled trials (involving 154 women) comparing surgical repair of first-degree (involving only the perineal or vaginal skin) or second-degree tears (also involving muscle) with leaving the wound to heal spontaneously. These trials showed no clear differences in clinical outcomes between the groups. The studies did not find any differences in pain immediately and up to eight weeks postpartum. One of the trials reported no difference in wounds complications, but the other showed differences in wound closure and poor wound approximation in the non-sutured group. There was no information about the effect on long-term outcomes such as sexual discomfort or incontinence. More research is needed to provide a strong evidence-based recommendation for clinical practice.\n",
      "\n",
      "\n",
      "Idx 66\n",
      "Eleven studies (1117 participants) met our inclusion criteria. These consisted of six case-control studies, two retrospective cohort studies and three prospective cohort studies. Three studies used single-headed camera SPECT while the remaining eight used multiple-headed camera SPECT. Study design and methods varied widely. Overall, participant selection was not well described and the studies were judged as having either high or unclear risk of bias. Often the threshold used to define a positive SPECT result was not predefined and the results were reported with knowledge of the reference standard. Concerns regarding applicability of the studies to the review question were generally low across all three domains (participant selection, index test and reference standard). Sensitivities and specificities for differentiating FTD from non-FTD ranged from 0.73 to 1.00 and from 0.80 to 1.00, respectively, for the three multiple-headed camera studies. Sensitivities were lower for the two single-headed camera studies; one reported a sensitivity and specificity of 0.40 (95% confidence interval (CI) 0.05 to 0.85) and 0.95 (95% CI 0.90 to 0.98), respectively, and the other a sensitivity and specificity of 0.36 (95% CI 0.24 to 0.50) and 0.92 (95% CI 0.88 to 0.95), respectively. Eight of the 11 studies which used SPECT to differentiate FTD from Alzheimer's disease used multiple-headed camera SPECT. Of these studies, five used a case-control design and reported sensitivities of between 0.52 and 1.00, and specificities of between 0.41 and 0.86. The remaining three studies used a cohort design and reported sensitivities of between 0.73 and 1.00, and specificities of between 0.94 and 1.00. The three studies that used single-headed camera SPECT reported sensitivities of between 0.40 and 0.80, and specificities of between 0.61 and 0.97. At present, we would not recommend the routine use of rCBF SPECT in clinical practice because there is insufficient evidence from the available literature to support this. Further research into the use of rCBF SPECT for differentiating FTD from other dementias is required. In particular, protocols should be standardised, study populations should be well described, the threshold for 'abnormal' scans predefined and clear details given on how scans are analysed. More prospective cohort studies that verify the presence or absence of FTD during a period of follow up should be undertaken.\n",
      "We searched many databases for all papers with FTD and rCBF SPECT as their focus. These papers were reviewed independently by several researchers. After application of inclusion and exclusion criteria, eleven studies including 299 individuals with FTD were available for this review. The studies were published over a 21-year period, with a study size ranging from 27 to 363 participants, mainly recruited from University clinics, tertiary referral centres or memory clinics. Of the 11 studies, three used single-headed (single detector) gamma cameras, a method no longer used in clinical practice today. Evidence is current to June 2013. The majority of studies were at high risk of bias due to insufficient details on how participants were selected and how the rCBF SPECT scans were conducted and analysed. The main limitations of the review were poor reporting, variability of study design and a lack of standardisation of image interpretation between centres. Due to small study numbers and large variation in how the studies were carried out, we are unable at present to recommend the routine use of rCBF SPECT for diagnosing FTD in clinical practice.\n",
      "\n",
      "\n",
      "Idx 67\n",
      "The 19 included trials (involving 1589 older adults) were small, often with methodological flaws. Just two pairs of trials tested similar interventions. Twelve trials evaluated mobilisation strategies started soon after hip fracture surgery. Single trials found improved mobility from, respectively, a two-week weight-bearing programme, a quadriceps muscle strengthening exercise programme and electrical stimulation aimed at alleviating pain. Single trials found no significant improvement in mobility from, respectively, a treadmill gait retraining programme, 12 weeks of resistance training, and 16 weeks of weight-bearing exercise. One trial testing ambulation started within 48 hours of surgery found contradictory results. One historic trial found no significant difference in unfavourable outcomes for weight bearing started at two versus 12 weeks. Of two trials evaluating more intensive physiotherapy regimens, one found no difference in recovery, the other reported a higher level of drop-out in the more intensive group. Two trials tested electrical stimulation of the quadriceps: one found no benefit and poor tolerance of the intervention; the other found improved mobility and good tolerance. Seven trials evaluated strategies started after hospital discharge. Started soon after discharge, two trials found improved outcome after 12 weeks of intensive physical training and a home-based physical therapy programme respectively. Begun after completion of standard physical therapy, one trial found improved outcome after six months of intensive physical training, one trial found increased activity levels from a one year exercise programme, and one trial found no significant effects of home-based resistance or aerobic training. One trial found improved outcome after home-based exercises started around 22 weeks from injury. One trial found home-based weight-bearing exercises starting at seven months produced no significant improvement in mobility. There is insufficient evidence from randomised trials to establish the best strategies for enhancing mobility after hip fracture surgery.\n",
      "This review includes evidence from 19 trials involving 1589 participants, generally aged over 65 years. Many of the trials had weak methods, including inadequate follow-up. There was no pooling of data because no two trials were sufficiently alike. Twelve trials evaluated interventions started soon after hip fracture surgery. Single trials found improved mobility from, respectively, a two-week weight-bearing programme, a quadriceps muscle strengthening exercise programme and electrical stimulation aimed at alleviating pain. Single trials found no significant improvement in mobility from, respectively, a treadmill gait retraining programme, 12 weeks of resistance training, and 16 weeks of weight-bearing exercise. One trial testing ambulation started within 48 hours of surgery found contradictory results. One historic trial found no significant difference in unfavourable outcomes for weight bearing started at two versus 12 weeks. Of two trials evaluating more intensive physiotherapy regimens, one found no difference in recovery, the other reported a higher level of drop-out in the more intensive group. Two trials tested electrical stimulation of the quadriceps: one found no benefit and poor tolerance of the intervention; the other found improved mobility and good tolerance. Seven trials evaluated interventions started after hospital discharge. Started soon after discharge, two trials found improved outcome after 12 weeks of intensive physical training and a home-based physical therapy programme respectively. Begun after completion of standard physical therapy, one trial found improved outcome after six months of intensive physical training, one trial found increased activity levels from a one year exercise programme, and one trial found no significant effects of home-based resistance or aerobic training. One trial found improved outcome after home-based exercises started around 22 weeks from injury. One trial found home-based weight-bearing exercises starting at seven months produced no significant improvement in mobility. In summary, the review found there was not enough evidence to determine which are the best strategies, started in hospital or after discharge from hospital, for helping people walk and continue walking after hip fracture surgery.\n",
      "\n",
      "\n",
      "Idx 68\n",
      "We included two randomized controlled trials (218 eyes of 216 participants) comparing the effectiveness of pneumatic retinopexy versus scleral buckle for eyes with RRD. We identified no studies investigating the comparison of pneumatic retinopexy versus a combination treatment of scleral buckle and vitrectomy. Of the two included studies, one was a small study with 20 participants enrolled in Ireland and followed for an average of 16 months. The second study was larger with 196 participants (198 eyes) enrolled in the United States and followed for at least 6 months. Cautious interpretation of the results is warranted, since we graded the evidence as low to moderate quality due to insufficient reporting of study methods and imprecision and inconsistency among study results. Both studies showed fewer eyes achieving retinal reattachment in the pneumatic retinopexy group compared with the scleral buckle group by six-months follow-up (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.77 to 1.02, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on reattachment because the results are imprecise. Eyes in the pneumatic retinopexy group also were more likely to have had a recurrence of retinal detachment by six-months follow-up (RR 1.80, 95% CI 1.00 to 3.24, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on recurrence because the lower CI equals no difference. Neither study reported mean change in visual acuity, quality of life data, or economic measures. Differences between the pneumatic retinopexy group and scleral buckle group were uncertain due to small numbers of events with respect to operative ocular adverse events (RR 0.67, 95% CI 0.32 to 1.42, 218 eyes), development of cataract (RR 0.92, 95% CI 0.06 to 14.54, 198 eyes), glaucoma (RR 0.31, 95% CI 0.03 to 2.91, 198 eyes), macular pucker (RR 0.74, 95% CI 0.20 to 2.67, 198 eyes), and proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96, 218 eyes). Fewer eyes in the pneumatic retinopexy group compared with the scleral buckle group experienced choroidal detachment (RR 0.17, 95% CI 0.05 to 0.57, 198 eyes) or myopic shift equal to or greater than 1 diopter spherical equivalent (RR 0.04, 95% CI 0.01 to 0.13, 198 eyes). The evidence suggests that pneumatic retinopexy may result in lower rates of reattachment and higher rates of recurrence than scleral buckle for eyes with RRD, but does not rule out no difference between procedures. The relative safety of the procedures is uncertain and the relative effects of these procedures in terms of other patient-important outcomes, such as visual acuity and quality of life, is unknown. Due to the limited information available between pneumatic retinopexy and scleral buckle procedures, future research addressing these evidence gaps are warranted.\n",
      "We found two randomized trials that had enrolled a total of 216 participants (218 eyes) from Ireland and the United States. Both studies evaluated whether pneumatic retinopexy or scleral buckle was a better treatment for RRD. The study in the US had 198 participants with 6 months to 2 years of follow-up. The study in Ireland had 20 participants with 5 to 27 months of follow-up. The evidence is current to 13 January 2015. Results from both studies suggested that scleral buckle may perform better or as well as pneumatic retinopexy in terms of reattachment rates and reducing the risk of recurrence of detachment. Few ocular adverse events occurred during either procedure and differences in some adverse events occurring after the surgeries could not be determined. More eyes in the scleral buckle group experienced choroidal detachment (separation of the choroid, the layer between the retina and sclera, from the sclera) and myopic shift (change to nearsightedness that may be a sign of developing cataract) than eyes in the pneumatic retinopexy group. The quality of the evidence was assessed as low to moderate due to poor reporting of how the studies were done. Further, there was lack of information regarding important outcomes that may be useful when choosing which procedure to use in terms of vision, quality of life, and cost.\n",
      "\n",
      "\n",
      "Idx 69\n",
      "We included 58 trials, involving 2797 participants, which comprised cardiorespiratory interventions (28 trials, 1408 participants), resistance interventions (13 trials, 432 participants), and mixed training interventions (17 trials, 957 participants). Thirteen deaths occurred before the end of the intervention and a further nine before the end of follow-up. No dependence data were reported. Diverse outcome measures restricted pooling of data. Global indices of disability show moderate improvement after cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) 0.19 to 0.84; P value = 0.002) and by a small amount after mixed training (SMD 0.26, 95% CI 0.04 to 0.49; P value = 0.02); benefits at follow-up (i.e. after training had stopped) were unclear. There were too few data to assess the effects of resistance training. Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 6.71 metres per minute, 95% CI 2.73 to 10.69), preferred gait speed (MD 4.28 metres per minute, 95% CI 1.71 to 6.84), and walking capacity (MD 30.29 metres in six minutes, 95% CI 16.19 to 44.39) at the end of the intervention. Mixed training, involving walking, increased preferred walking speed (MD 4.54 metres per minute, 95% CI 0.95 to 8.14), and walking capacity (MD 41.60 metres per six minutes, 95% CI 25.25 to 57.95). Balance scores improved slightly after mixed training (SMD 0.27, 95% CI 0.07 to 0.47). Some mobility benefits also persisted at the end of follow-up. The variability, quality of the included trials, and lack of data prevents conclusions about other outcomes and limits generalisability of the observed results. Cardiorespiratory training and, to a lesser extent, mixed training reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve the speed and tolerance of walking; some improvement in balance could also occur. There is insufficient evidence to support the use of resistance training. The effects of training on death and dependence after stroke are still unclear but these outcomes are rarely observed in physical fitness training trials. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription and identify long-term benefits.\n",
      "By February 2015 we identified 58 trials for inclusion in the review. The trials involved at total of 2797 participants at all stages of care including being in hospital or back living at home. Most of the people who took part were able to walk on their own. The trials tested different forms of fitness training; these included 1) cardiorespiratory or 'endurance' training, 2) resistance or 'strength' training, or 3) mixed training, which is a combination of cardiorespiratory plus resistance training. We found that cardiorespiratory fitness training, particularly involving walking, can improve exercise ability and walking after stroke. Mixed training improves walking ability and improves balance. However, there was not enough information to draw reliable conclusions about the impact of fitness training on other areas such as quality of life, mood, or cognitive function. Cognitive function is under-investigated despite being a key outcome of interest for stroke survivors. There was no evidence that any of the different types of fitness training caused injuries or other health problems; exercise appears to be a safe intervention. We need more studies to examine the benefits that are important to stroke survivors, in particular for those with more severe stroke who are unable to walk. Studies of fitness training can be difficult to carry out. This means most of the studies were small and of moderate quality. However, some consistent findings did emerge with different studies all tending to show the same effect.\n",
      "\n",
      "\n",
      "Idx 70\n",
      "Sixteen studies (894 patients) were included. No formulation, route, or schedule of vitamin D compound was found to alter the mortality risk or need for dialysis. Vitamin D compounds significantly lowered serum PTH (4 studies, 153 patients: MD -49.34 pg/mL, 95% CI -85.70 to -12.97 (-5.6 pmol/L, 95% CI -9.77 to -1.48)) and were more likely to reduce serum PTH > 30% from baseline value (264 patients: RR 7.87, 95% CI 4.87 to 12.73). Vitamin D treatment was associated with increased end of treatment serum phosphorus (3 studies, 140 patients: MD 0.37 mg/dL, 95% CI 0.09, 0.66 (0.12 mmol/L, 95% CI 0.03, 0.21)) and serum calcium (5 studies, 184 patients: MD 0.20 mg/dL, 95% CI 0.17 to 0.23 (0.05 mmol/L, 95% CI 0.04 to 0.06)). Few data were available comparing intermittent with daily vitamin D administration, or other schedules of dosing. There are not sufficient data to determine the effect of vitamin D compounds on mortality and cardiovascular outcomes in people with CKD not requiring dialysis. While vitamin D compounds reduce serum PTH (49.3 pg/mL (5.6 pmol/L)) compared with placebo, the relative clinical benefits of PTH lowering versus treatment-related increases in serum phosphorus and calcium remain to be understood.\n",
      "We identified 16 studies of vitamin D preparations in people with CKD and not requiring dialysis (less severe CKD) involving 894 people. No studies were designed to understand the effect of vitamin D therapy on risks of premature cardiovascular disease or mortality. Vitamin D agents lowered PTH significantly compared with no treatment, however also increased both calcium and phosphorus levels. Newer vitamin D therapies have not been compared with older vitamin compounds in CKD directly; whether they are associated with increased calcium and phosphorus is uncertain. In the future, new studies are required to assess outcomes important to patients, such as life expectancy and premature heart disease. It will also be important to know if vitamin D therapy should be used differently (differing target levels of PTH) in differing stages of CKD.\n",
      "\n",
      "\n",
      "Idx 71\n",
      "Sixteen trials, involving over one million adults, children and infants, fulfilled the inclusion criteria. Twenty-four comparisons reported on vaccine efficacy (cholera cases and/or deaths) and 11 comparisons considered adverse effects (nine reported on both). Compared to placebo, vaccinees had a reduced risk of death from cholera (RR 0.49, 95% CI 0.25 to 0.93; 837,442 participants) and a reduced risk of contracting cholera at 12 months (RR 0.52, 95% CI 0.42 to 0.65, random-effects model; 1,512,573 participants). This translates to an efficacy of 48%, 95% confidence interval 35% to 58%. Significant protection lasted for two years, even after only a single dose, and for three years with an annual booster. Children over five years and adults were protected for up to three years, while children under five years were protected for up to a year. Injected cholera vaccines were associated with more systemic and local adverse effects compared to placebo, but these were not severe or life-threatening. Injected cholera vaccines appear to be safe and relatively more effective than usually realized. Protection against cholera persists for up to two years following a single dose of vaccine, and for three years with an annual booster. However, they have been superseded by oral vaccines.\n",
      "Sixteen trials, involving over one million adults, children, and infants, were included. Injected cholera vaccines reduced the risk of death from cholera and the risk of contracting cholera at 12 months. Significant protection lasted for two years. Injected cholera vaccines had more systemic and local adverse effects than placebo, but these adverse effects were relatively well tolerated and were not severe or life-threatening. The authors conclude that injected cholera vaccines appear to be relatively safe and more effective than usually realized. However, they are not currently available and therefore cannot be recommended for use. This review provides a solid background of evidence for the effects of cholera injected vaccines, against which to compare the effects of oral vaccines.\n",
      "\n",
      "\n",
      "Idx 72\n",
      "We included two trials with 215 participants. One trial was published in 2011 and included 193 children aged 9 months to 18 months, and compared treatment with hydroxyurea to placebo. The second trial was published in 1998 and included 22 adults with normal blood pressure and microalbuminuria and compared ACEI to placebo. We rated the quality of evidence as low to very low across different outcomes according to GRADE methodology. This was due to trials having: a high or unclear risk of bias including attrition and detection bias; indirectness (the available evidence was for children aged 9 months to 18 months in one trial and a small and select adult sample size in a second trial); and imprecise outcome effect estimates of significant benefit or harm. Hydroxyurea versus placebo We are very uncertain if hydroxyurea reduces or prevents progression of kidney disease (assessed by change in glomerular filtration rate), or reduces hyperfiltration in children aged 9 to 18 months, mean difference (MD) 0.58 (95% confidence interval (CI) -14.60 to 15.76 (mL/min per 1.73 m²)) (one study; 142 participants; very low-quality evidence). In children aged 9 to 18 months, hydroxyurea may improve the ability to concentrate urine, MD 42.23 (95% CI 12.14 to 72.32 (mOsm/kg)) (one study; 178 participants; low-quality evidence). Hydroxyurea may make little or no difference to SCD-related serious adverse events including: incidence of acute chest syndrome, risk ratio (RR) 0.39 (99% CI 0.13 to 1.16); painful crisis, RR 0.68 (99% CI 0.45 to 1.02); and hospitalisations, RR 0.83 (99% CI 0.68 to 1.01) (one study, 193 participants; low-quality evidence). No deaths occurred in the trial. Quality of life was not reported. ACEI versus placebo We are very uncertain if ACEI reduces proteinuria in adults with SCD who have normal blood pressure and microalbuminuria, MD -49.00 (95% CI -124.10 to 26.10 (mg per day)) (one study; 22 participants; very low-quality evidence). We are very uncertain if ACEI reduce or prevent kidney disease as measured by creatinine clearance. The authors state that creatinine clearance remained constant over six months in both groups, but no comparative data were provided (very low-quality evidence). All-cause mortality, serious adverse events and quality of life were not reported. In young children aged 9 months to 18 months, we are very uncertain if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration, but it may improve young children's ability to concentrate urine and may make little or no difference on the incidence of acute chest syndrome, painful crises and hospitalisations. We are very uncertain if giving ACEI to adults with normal blood pressure and microalbuminuria has any effect on preventing or reducing kidney complications. This review identified no trials that looked at red cell transfusions nor any combinations of interventions to prevent or reduce kidney complications. Due to lack of evidence this review cannot comment on the management of either children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately-designed and powered studies, and no ongoing trials which address this critical question. Trials of hydroxyurea, ACEI or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction kidney complications in people with SCD.\n",
      "We found two randomised controlled trials which enrolled a total of 215 participants. One trial, published in 2011, was conducted in 193 infants aged 9 months to 18 months and compared the drug hydroxyurea to placebo. The second trial, published in 1998, was conducted in 22 adults with normal blood pressure and microalbuminuria (an increase of protein in the urine) and compared captopril (a drug used to treat high blood pressure) to placebo. Both trials received government funding. In infants aged 9 months to 18 months, hydroxyurea may increase the ability to produce normal urine, but we are very uncertain if it has any effect on the glomerular filtration rate (network of filters in the kidney that filter waste from the blood). Hydroxyurea may make little or no difference on the incidence of SCD-related serious complications (including acute chest syndrome, painful crises and hospitalisations). We are very uncertain if giving captopril to adults with SCD who have normal blood pressure and early signs of kidney damage (microalbuminuria) reduces progression of kidney damage. Quality of life was not reported in either trial. The evidence for all outcomes was rated as low- to very low-quality due to trials being at high risk of bias and because there were a small number of trials and a small number of participants included in the trials.\n",
      "\n",
      "\n",
      "Idx 73\n",
      "Five trials with 196 people were included. One three-arm trial (47 participants) compared arthrographic distension using steroid and air to distension using air alone and to steroid injection alone. One trial (46 participants) compared arthrographic distension using steroid and saline to placebo. Two trials (45 and 22 participants) compared arthrographic distension using steroid to steroid injection alone. One trial (36 participants) compared arthrographic distension using steroid and saline plus physical therapy to physical therapy alone. Trials included similar study participants, but quality and reporting of data were variable. Only one trial was at low risk of bias. No meta-analysis was performed. The trial with low risk of bias demonstrated that distension with saline and steroid was better than placebo for pain (number needed to treat to benefit (NNTB) = 2), function (NNTB = 3) and range of movement at three weeks. This benefit was maintained at six and 12 weeks only for one of two scores measuring function (NNT = 3). A second trial with high risk of bias also reported that distension combined with physical therapy improved range of movement and median percent improvement in pain (but not pain score) at eight weeks compared to physical therapy alone. Three further trials, all at high risk of bias, reported conflicting, variable effects of arthrographic distension with steroid compared to distension alone, and arthrographic distension with steroid compared to intra-articular steroid injection. The trials reported a small number of minor adverse effects, mainly pain during and after the procedure. There is \"silver\" level evidence that arthrographic distension with saline and steroid provides short-term benefits in pain, range of movement and function in adhesive capsulitis. It is uncertain whether this is better than alternative interventions.\n",
      "Disability: One study found that at three weeks after treatment, people's disability was improved by 11 points on a scale of 0-100, possibly as few as 4 or as many as 11 points on a scale of 0-100. Another study found disability was improved by 17 points. This improvement could possibly be as low as 6 or as many as 28 points on a scale of 0-100. At six weeks after treatment, people's disability was improved by 46 points on a scale of 0-500. This improvement could possibly be as little as 20 points or as many as 80 points on a scale of 0-500. At 12 weeks after treatment, people's disability was improved by 54 points on a scale of 0-500. This improvement could be as little as 15 points or as many as 95 points on a scale of 0-500. The numbers given are our best estimate. When possible, we have also presented a range because there is a 95 percent chance that the true effect of the treatment lies somewhere between that range.\n",
      "\n",
      "\n",
      "Idx 74\n",
      "We included six trials (483 adult ICU participants). Exercise-based interventions were delivered on the ward in two studies; both on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay following ICU discharge (up to a fixed duration of 12 weeks). Risk of bias was variable for all domains across all trials. High risk of bias was evident in all studies for performance bias, although blinding of participants and personnel in therapeutic rehabilitation trials can be pragmatically challenging. For other domains, at least half of the studies were at low risk of bias. One study was at high risk of selection bias, attrition bias and other sources of bias. Risk of bias was unclear for the remaining studies across domains. We decided not to undertake a meta-analysis because of variation in study design, types of interventions and outcome measurements. We present a narrative description of individual studies for each outcome. All six studies assessed functional exercise capacity, although we noted wide variability in the nature of interventions, outcome measures and associated metrics and data reporting. Overall quality of the evidence was very low. Individually, three studies reported positive results in favour of the intervention. One study found a small short-term benefit in anaerobic threshold (mean difference (MD) 1.8 mL O2/kg/min, 95% confidence interval (CI) 0.4 to 3.2; P value = 0.02). In a second study, both incremental (MD 4.7, 95% CI 1.69 to 7.75 watts; P value = 0.003) and endurance (MD 4.12, 95% CI 0.68 to 7.56 minutes; P value = 0.021) exercise testing results were improved with intervention. Finally self reported physical function increased significantly following use of a rehabilitation manual (P value = 0.006). Remaining studies found no effect of the intervention. Similar variability was evident with regard to findings for the primary outcome of health-related quality of life. Only two studies evaluated this outcome. Individually, neither study reported differences between intervention and control groups for health-related quality of life due to the intervention. Overall quality of the evidence was very low. Four studies reported rates of withdrawal, which ranged from 0% to 26.5% in control groups, and from 8.2% to 27.6% in intervention groups. The quality of evidence for the effect of the intervention on withdrawal was low. Very low-quality evidence showed rates of adherence with the intervention. Mortality ranging from 0% to 18.8% was reported by all studies. The quality of evidence for the effect of the intervention on mortality was low. Loss to follow-up, as reported in all studies, ranged from 0% to 14% in control groups, and from 0% to 12.5% in intervention groups, with low quality of evidence. Only one non-mortality adverse event was reported across all participants in all studies (a minor musculoskeletal injury), and the quality of the evidence was low. At this time, we are unable to determine an overall effect on functional exercise capacity, or on health-related quality of life, of an exercise-based intervention initiated after ICU discharge for survivors of critical illness. Meta-analysis of findings was not appropriate because the number of studies and the quantity of data were insufficient. Individual study findings were inconsistent. Some studies reported a beneficial effect of the intervention on functional exercise capacity, and others did not. No effect on health-related quality of life was reported. Methodological rigour was lacking across several domains, influencing the quality of the evidence. Wide variability was noted in the characteristics of interventions, outcome measures and associated metrics and data reporting. If further trials are identified, we may be able to determine the effects of exercise-based intervention following ICU discharge on functional exercise capacity and health-related quality of life among survivors of critical illness.\n",
      "We included six studies that involved 483 participants (298 male, 185 female) over the age of 18 years. Participants had received breathing support from a machine (been mechanically ventilated) for longer than 24 hours whilst in the ICU and had begun an exercise programme after leaving the ICU. Studies were carried out in the UK, Australia, the USA and Italy. Exercise programmes were delivered on the ward in two studies; on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay after ICU discharge up to a fixed time of 12 weeks. Exercises included arm or leg cycling, walking and general muscle strengthening at home, provision of self help manuals and hospital-based multi-exercise programmes carried out in physiotherapist-led gymnasiums. Three of the six studies were funded by government health research funding agencies. One study was supported by combined funding from an independent charity and a commercial company (with no interest in the results of the study). One study did not report a funding source, and another was funded by an academic health research agency. We were unable to determine an overall result for the effects of exercise-based interventions. Three studies reported improvement in functional exercise capacity following completion of the exercise programme, and the other three found no effects of treatment. Only two studies measured patient-reported health-related quality of life, and both of these studies showed no effects related to treatment. Again, we were unable to reach an overall conclusion. No study included an evaluation of acceptance of the treatment by patients or the experience of patient participation in an exercise-based programme. We found considerable differences across included studies regarding types of exercise, how measurements of functional exercise capacity were collected, ways by which results were presented and people who had been critically ill. Exercise programmes were compared with usual care, with lack of acknowledgement of the standard level of rehabilitation and exercise in usual practice. In addition, we found variability in how well the studies were performed. We were unable to perform any statistical tests on study findings or to make firm conclusions because of this variability. The overall quality of the evidence was very low for these reasons. . Evidence is current to May 2014. We reran the search in February 2015 and will deal with studies of interest when we update the review.\n",
      "\n",
      "\n",
      "Idx 75\n",
      "We included 12 trials with 734 patients randomised to miniport laparoscopic cholecystectomy (380 patients) versus standard laparoscopic cholecystectomy (351 patients). Only one trial which included 70 patients was of low risk of bias. Miniport laparoscopic cholecystectomy could be completed successfully in more than 80% of patients in most trials. The remaining patients were mostly converted to standard port laparoscopic cholecystectomy but some were also converted to open cholecystectomy. These patients were included for the outcome conversion to open cholecystectomy but excluded from other outcomes. Accordingly, the results of the other outcomes are on 343 patients in the miniport laparoscopic cholecystectomy group and 351 patients in the standard port laparoscopic cholecystectomy group, and therefore the results have to be interpreted with extreme caution. There was no mortality in the seven trials that reported mortality (0/194 patients in miniport laparoscopic cholecystectomy versus 0/203 patients in standard port laparoscopic cholecystectomy). There were no significant differences between miniport laparoscopic cholecystectomy and standard laparoscopic cholecystectomy in the proportion of patients who developed serious adverse events (eight trials; 460 patients; RR 0.33; 95% CI 0.04 to 3.08) (miniport laparoscopic cholecystectomy: 1/226 (adjusted proportion 0.4%) versus standard laparoscopic cholecystectomy: 3/234 (1.3%); quality of life at 10 days after surgery (one trial; 70 patients; SMD -0.20; 95% CI -0.68 to 0.27); or in whom the laparoscopic operation had to be converted to open cholecystectomy (11 trials; 670 patients; RR 1.23; 95% CI 0.44 to 3.45) (miniport laparoscopic cholecystectomy: 8/351 (adjusted proportion 2.3%) versus standard laparoscopic cholecystectomy 6/319 (1.9%)). Miniport laparoscopic cholecystectomy took five minutes longer to complete than standard laparoscopic cholecystectomy (12 trials; 695 patients; MD 4.91 minutes; 95% CI 2.38 to 7.44). There were no significant differences between miniport laparoscopic cholecystectomy and standard laparoscopic cholecystectomy in the length of hospital stay (six trials; 351 patients; MD -0.00 days; 95% CI -0.12 to 0.11); the time taken to return to activity (one trial; 52 patients; MD 0.00 days; 95% CI -0.31 to 0.31); or in the time taken for the patient to return to work (two trials; 187 patients; MD 0.28 days; 95% CI -0.44 to 0.99) between the groups. There was no significant difference in the cosmesis scores at six months to 12 months after surgery between the two groups (two trials; 152 patients; SMD 0.13; 95% CI -0.19 to 0.46). Miniport laparoscopic cholecystectomy can be completed successfully in more than 80% of patients. There appears to be no advantage of miniport laparoscopic cholecystectomy in terms of decreasing mortality, morbidity, hospital stay, return to activity, return to work, or improving cosmesis. On the other hand, there is a modest increase in operating time after miniport laparoscopic cholecystectomy compared with standard port laparoscopic cholecystectomy and the safety of miniport laparoscopic cholecystectomy is yet to be established. Miniport laparoscopic cholecystectomy cannot be recommended routinely outside well-designed randomised clinical trials. Further trials of low risks of bias and low risks of random errors are necessary.\n",
      "We identified 12 randomised clinical trials involving 734 patients that compared miniport laparoscopic cholecystectomy (380) with standard port laparoscopic cholecystectomy (351). The choice of the treatment that the patients received was determined by a method similar to toss of coin so that both treatments were conducted in patients who were as similar as possible. Most of the trials were of high risk of bias, i.e. there is possibility of arriving at wrong conclusions overestimating benefits or underestimating harms because of study design. Miniport laparoscopic cholecystectomy could be completed successfully in more than 80% of patients in most studies. The remaining patients were mostly converted to standard port laparoscopic cholecystectomy but some patients had to undergo open cholecystectomy. These patients were excluded from the analysis by the study authors and so the results of these trials as well as the present systematic review have to be interpreted with extreme caution. There was no mortality in either group in the seven trials that reported mortality (0/226 patients versus 0/234 patients). There were no significant differences between the two operation types in the proportion of patients who developed serious complications, quality of life at 10 days after operation, or in whom the laparoscopic operation had to be converted to open cholecystectomy. Miniport laparoscopic cholecystectomy took five minutes longer to complete than standard port laparoscopic cholecystectomy. There were no significant differences between the two operation types in the length of hospital stay, the time taken to return to activity, or in the time taken to return to work. There was no significant cosmetic difference at six months to 12 months after surgery between the two groups, in the two trials that reported this outcome. There appears to be no advantage of miniport laparoscopic cholecystectomy in terms of decreasing surgical complications, hospital stay, return to activity, return to work, or improving cosmesis. On the other hand, there is a modest increase in operating time after miniport laparoscopic cholecystectomy compared with standard port laparoscopic cholecystectomy. The safety of miniport laparoscopic cholecystectomy is yet to be established. Miniport laparoscopic cholecystectomy cannot be recommended routinely outside well-designed randomised clinical trials. Further well-designed randomised clinical trials are necessary to determine whether miniport laparoscopic cholecystectomy is safe and whether there is any advantage over standard port laparoscopic cholecystectomy.\n",
      "\n",
      "\n",
      "Idx 76\n",
      "We identified two RCTs and one CCT (total number of participants 149) evaluating the use of amifostine versus no additional treatment in the original version of the review; the updates identified no additional studies. Two studies included children with osteosarcoma, and the other study included children with hepatoblastoma. Children received cisplatin only or a combination of cisplatin and carboplatin, either intra-arterially or intravenously. Pooling of results of the included studies was not possible. From individual studies the effect of amifostine on symptomatic ototoxicity only (i.e. National Cancer Institute Common Toxicity Criteria version 2 (NCICTCv2) or modified Brock grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (i.e. NCICTCv2 or modified Brock grade 1 or higher) were uncertain (low-certainty evidence). Only one study including children with osteosarcoma treated with intra-arterial cisplatin provided information on tumour response, defined as the number of participants with a good or partial remission. The available-data analysis (data were missing for one participant), best-case scenario analysis and worst-case scenario analysis showed a difference in favour of amifostine, although the certainty of evidence for this effect was low. There was no information on survival for any of the included studies. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided data on the number of participants with adverse effects other than ototoxicity grade 3 or higher (on NCICTCv2 scale). There was low-certainty evidence that grade 3 or 4 vomiting was higher with amifostine (risk ratio (RR) 9.04, 95% confidence interval (CI) 1.99 to 41.12). The effects on cardiotoxicity and renal toxicity grade 3 or 4 were uncertain (low-certainty evidence). None of the studies evaluated quality of life. In the recent update, we also identified one RCT including 109 children with localized hepatoblastoma evaluating the use of sodium thiosulfate versus no additional treatment. Children received intravenous cisplatin only (one child also received carboplatin). There was moderate-certainty evidence that both symptomatic ototoxicity only (i.e. Brock criteria grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (i.e. Brock criteria grade 1 or higher) was lower with sodium thiosulfate (combined asymptomatic and symptomatic ototoxicity: RR 0.52, 95% CI 0.33 to 0.81; symptomatic ototoxicity only: RR 0.39, 95% CI 0.19 to 0.83). The effect of sodium thiosulfate on tumour response (defined as number of participants with a complete or partial response at the end of treatment), overall survival (calculated from time of randomization to death or last follow-up), event-free survival (calculated from time of randomization until disease progression, disease relapse, second primary cancer, death, or last follow-up, whichever came first) and adverse effects other than hearing loss and tinnitus grade 3 or higher (according to National Cancer Institute Common Toxicity Criteria Adverse Effects version 3 (NCICTCAEv3) criteria) was uncertain (low-certainty evidence for all these outcomes). Quality of life was not assessed. We found no eligible studies for possible otoprotective medical interventions other than amifostine and sodium thiosulfate and for other types of malignancies. At the moment there is no evidence from individual studies in children with osteosarcoma or hepatoblastoma treated with different platinum analogues and dosage schedules that underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment. Since pooling of results was not possible and the evidence was of low certainty, no definitive conclusions can be made. Since we found only one RCT evaluating the use of sodium thiosulfate in children with localized hepatoblastoma treated with cisplatin, no definitive conclusions on benefits and harms can be drawn. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. We identified no eligible studies for other possible otoprotective medical interventions and other types of malignancies, so no conclusions can be made about their efficacy in preventing ototoxicity in children treated with platinum-based therapy. More high-quality research is needed.\n",
      "The evidence is current to January 2019. We found two randomized studies (clinical studies where people are randomly put into one of two or more treatment groups) and one controlled study (clinical studies where people are put into one of two or more treatment groups but this is not done in a random way) (149 participants), all comparing amifostine with no additional treatment. Two studies included children with osteosarcoma (a type of bone cancer), the other study included children with hepatoblastoma (a type of liver cancer). Combining the results of the included studies was not possible. It is not clear how long participants were monitored. We also found one randomized study (109 children with localized hepatoblastoma) comparing sodium thiosulfate with no additional treatment. Half of the participants were monitored for more than four years. At the moment there is no evidence from individual studies showing that the use of amifostine prevents hearing loss. Only one study reported results on cancer response and side effects, so we could make no definitive conclusions. None of the studies assessed survival and quality of life. Hearing loss seemed to be lower with the use of sodium thiosulfate, but the effect of sodium thiosulfate on cancer response and side effects was uncertain. We identified no adequate studies for other possible drugs to prevent hearing loss and for other types of cancer. Before definitive conclusions can be made about the usefulness of possible medicines to prevent hearing loss (amifostine, sodium thiosulfate or another medicine) in children treated with platinum chemotherapy more high-quality research is needed. The quality of the evidence was moderate (for hearing loss with sodium thiosulfate) to low (for all other outcomes (results)). The quality of the evidence was limited because of issues with the study design (for all outcomes) and small numbers of participants in each study (for all outcomes except hearing loss with sodium thiosulfate).\n",
      "\n",
      "\n",
      "Idx 77\n",
      "Six trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INFα-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INFα-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INFα-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13). The reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf α-2a (high dose) and 5-FU + CO2 Laser + Inf α-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.\n",
      "This review evaluated the effectiveness and safety of topical 5-FU for treatment of genital warts in nonimmunocompromised individuals. Evidence from the studies we reviewed showed that 5-FU had better results for cure than placebo or no treatment; MCSA; and Podophylin 2%, 4% or 25%. No statistical difference was found when 5-FU was compared with CO2 Laser treatment, and results were poor when 5-FU was compared with 5-FU + INFα-2a (high dose) or 5-FU + CO2 Laser INFα-2a (high dose). The weak point of this review was the great variability in the methods and quality of the studies that we included.\n",
      "\n",
      "\n",
      "Idx 78\n",
      "Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests. Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)). All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear. None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.\n",
      "The evidence included in this review is current to April 2015. We included 11 studies on combinations of several testing methods involving 1339 participants. All studies evaluated women of reproductive age who were undertaking diagnostic surgery to investigate symptoms of endometriosis or for other indications. Fifteen combinations of different blood, endometrial and urinary biomarkers were studied, incorporating ultrasound, clinical history and examination. Each combination of tests was assessed in small individual studies. Several studies identified the combined tests that might be of value in diagnosing endometriosis, but there are too few reports to be sure of their diagnostic benefit. The reports were of low methodological quality, which is why these results cannot be considered reliable unless confirmed in large high-quality studies. Overall, there is not enough evidence to demonstrate benefit of any combined non-invasive test for use in clinical practice for the diagnosis of endometriosis over the current ‘gold standard’ of diagnostic laparoscopy. More high-quality research studies are needed to accurately assess the diagnostic potential of any type of non-invasive tests or their combinations that were identified in only a few studies as possibly having value in the detection of endometriosis.\n",
      "\n",
      "\n",
      "Idx 79\n",
      "Only three trials, involving 189 participants, satisfied the inclusion criteria and these were of low methodological quality. One study showed a significant difference in hearing recovery in the vasodilator group (carbogen combined with a course of several other drugs) compared to the control group (a course of several other drugs alone). Another study only showed a significant improvement in higher frequencies in the vasodilator group (prostaglandin E1 + steroid) compared with the control group (placebo and steroid), no difference having been shown in overall hearing gain. In the third study the vasodilator group (naftidrofuryl and low-molecular weight dextran) showed an improvement only in lower frequencies over the control group (placebo and low-molecular weight dextran). Two of the studies reported adverse effects from vasodilator treatment, whereas there was no mention of any side effects in the third. Five patients in one study developed a sensation of heaviness in the head which settled spontaneously and did not interfere with treatment. In the other study one patient developed an allergic reaction and had to be excluded from the study. The effectiveness of vasodilators in the treatment of ISSHL remains unproven. The included studies were of relatively poor quality and the number of patients included was small. Moreover, there were differences in the type, dosage and duration of vasodilator used in each study. Due to the degree of heterogeneity the results could not be combined to reach a conclusion.\n",
      "We found three trials, involving 189 participants, which showed improvement in hearing thresholds in those treated with vasodilators compared to control groups. However, as the number of patients included in the studies was small, and there were differences in the type, dosage and duration of vasodilator treatment used in each of these studies, the results could not be combined to reach a conclusion. The effectiveness of vasodilators in the treatment of ISSHL could not be proven. Further research is needed.\n",
      "\n",
      "\n",
      "Idx 80\n",
      "One trial involving 104 adult RRMS patients with an entry score ≤ 5.0 on the Expanded Disability Status Scale (EDSS) and at least one relapse during the preceding year was included. This trial evaluated rituximab as monotherapy versus placebo, with a single course of 1000 mg intravenous rituximab (on day 1 and day 15). A significant attrition bias was found at week 48 (24.0%). Patients receiving rituximab had a significant reduction in total number of gadolinium-enhancing lesions at week 24 (mean number 0.5 versus 5.5; relative reduction 91%) and in annualised rate of relapse at week 24 (0.37 versus 0.84) but not at week 48 (0.37 versus 0.72). Disability progression was not included as an outcome in this trial. More patients in the rituximab group had adverse events within the 24 hours after the first infusion (78.3% versus 40.0%), such as chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to-moderate events (92.6%). The most common infection-associated adverse events (> 10% in the rituximab group) were nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. Among them, only urinary tract infections (14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. One ongoing trial was identified. There is not sufficient evidence to support the use of rituximab as a disease-modifying therapy for RRMS because only one RCT was included. The quality of the study was limited due to high attrition bias, the small number of participants, and short follow-up. The beneficial effects of rituximab for RRMS remain inconclusive. However, short-term treatment with a single course of rituximab was safe for most patients with RRMS. Mild-to-moderate infusion-associated adverse events were common, as well as nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. The potential benefits of rituximab for treating RRMS need to be evaluated in large-scale studies that are of high quality along with long-term safety.\n",
      "Recent studies showed that a class of white blood cells (B lymphocytes) can be involved in the pathology of MS. This feature has led to a renewed interest in therapies directed at controlling B-cell activity. Rituximab belongs to the class of monoclonal antibodies and is able to diminish the number of B lymphocytes in the cerebrospinal fluid. The authors of this review assessed the efficacy and safety of rituximab in patients with RRMS, taking into account relapses, brain lesions and disease progression. From the pertinent literature, only one study evaluating rituximab versus placebo in 104 adult patients with at least one relapse during the preceding year was included. The authors did not find convincing evidence to support rituximab as an effective treatment for RRMS, also because the quality of the one identified study was limited due to high attrition bias, the small number of participants, and short follow-up. As far as safety is concerned, patients reported infusion-associated adverse events within the 24 hours after the first infusion, including chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation and pharyngolaryngeal pain. Among infection-associated adverse events, only urinary tract infections (in 14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. The potential benefits of rituximab for treating RRMS need to be further evaluated in large-scale studies that are of high quality along with long-term safety.\n",
      "\n",
      "\n",
      "Idx 81\n",
      "We included three RCTs (351 participants) that had moderate to high risk of bias. The quality of the evidence was very low for all outcomes. We downgraded the studies because of limitations in study design or execution (risk of bias), imprecision and inconsistency of results. We included a new trial presented only as a conference abstract in this update. In one study of acute laryngitis in adults, 100 participants were randomised to receive penicillin V (800 mg twice daily for five days) or an identical placebo. A recording of each patient reading a standardised text was made at the first visit, during re-examination after one and two weeks, and at follow-up after two to six months. No significant differences were found between the groups. The trial also measured symptoms reported by participants and found no significant differences. One study investigated erythromycin for acute laryngitis in 106 adults. The mean objective voice scores measured at the first visit, at re-examination after one and two weeks, and at follow-up after two to six months did not significantly differ between the groups. At one week there were significant beneficial differences in the severity of reported vocal symptoms (slight, moderate and severe) as judged by participants (P value = 0.042). However, the rates of participants having improved voice disturbance (subjective symptoms) at one and two weeks were not significantly different among groups. Comparing erythromycin and placebo groups on the rate of persistence of cough at two weeks, the risk ratio (RR) was 0.38 (95% confidence interval (CI) 0.15 to 0.97, P value = 0.04) and the number needed to treat for an additional beneficial outcome (NNTB) was 5.87 (95% CI 3.09 to 65.55). We calculated a RR of 0.64 (95% CI 0.46 to 0.90, P value = 0.034) and a NNTB of 3.76 (95% CI 2.27 to 13.52; P value = 0.01) for the subjective voice scores at one week. A third trial from Russia included 145 patients with acute laryngitis symptoms. Participants were randomised to three treatment groups: Group 1: seven-day course of fusafungine (six times a day by inhalation); Group 2: seven-day course of fusafungine (six times a day by inhalation) plus clarithromycin (250 mg twice daily for seven days); Group 3: no treatment. Clinical cure rates were measured at days 5 ± 1, 8 ± 1 and 28 ± 2. The authors reported significant differences in the rates of clinical cure at day 5 ± 1 favouring fusafungine (one trial; 93 participants; RR 1.50, 95% CI 1.02 to 2.20; P value = 0.04) and fusafungine plus clarithromycin (one trial 97 participants; RR 1.47, 95% CI 1.00 to 2.16; P value = 0.05) when compared to no treatment. However, no significant differences were found at days 8 ± 1 and 28 ± 2. Also, no significant differences were found when comparing fusafungine to fusafungine plus clarithromycin at days 5 ± 1, 8 ± 1 and 28 ± 2. Antibiotics do not appear to be effective in treating acute laryngitis when assessing objective outcomes. They appear to be beneficial for some subjective outcomes. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. Fusafungine could increase the cure rate at day five. The included RCTs had important methodological problems and these modest benefits from antibiotics may not outweigh their cost, adverse effects or negative consequences for antibiotic resistance patterns.\n",
      "This review found three studies involving 351 participants evaluating the effectiveness of different antibiotic therapies in adults with acute laryngitis. The evidence is current to December 2014. We ranked the quality of the evidence as low to very low, mainly because many studies had methodological limitations, outcome results were based on limited numbers of trials and the trials included participants that could not be pooled. We found that penicillin V and erythromycin appear to have no benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. Fusafungine could improve the rates of cured patients at day five. Overall, there is no clear benefit for the primary outcome, which is an objective assessment of voice quality, but some improvements are seen in subjective measures (i.e. cough, hoarseness of voice) that could be important to patients. However, we consider that these modest benefits from antibiotics may not outweigh their cost, adverse effects or negative consequences for antibiotic resistance patterns. The implications for practice are that prescribing antibiotics should not be done in the first instance as they will not objectively improve symptoms\n",
      "\n",
      "\n",
      "Idx 82\n",
      "Thirty-five randomised controlled trials, one ongoing, involving 5796 participants met the criteria for inclusion in this review. Included studies assessed the efficacy of tobacco cessation interventions, including counselling, and pharmacotherapy consisting of nicotine replacement therapy (NRT) or non-NRT, or the two combined, in both inpatient and outpatient settings for participants in treatment and in recovery. Most studies did not report information to assess the risk of allocation, selection, and attrition bias, and were classified as unclear. Analyses considered the nature of the intervention, whether participants were in treatment or recovery and the type of dependency. Of the 34 studies included in the meta-analysis, 11 assessed counselling, 11 assessed pharmacotherapy, and 12 assessed counselling in combination with pharmacotherapy, compared to usual care or no intervention. Tobacco cessation interventions were significantly associated with tobacco abstinence for two types of interventions. Pharmacotherapy appeared to increase tobacco abstinence (RR 1.88, 95% CI 1.35 to 2.57, 11 studies, 1808 participants, low quality evidence), as did combined counselling and pharmacotherapy (RR 1.74, 95% CI 1.39 to 2.18, 12 studies, 2229 participants, low quality evidence) at the period of longest follow-up, which ranged from six weeks to 18 months. There was moderate evidence of heterogeneity (I2 = 56% with pharmacotherapy and 43% with counselling plus pharmacotherapy). Counselling interventions did not significantly increase tobacco abstinence (RR 1.33, 95% CI 0.90 to 1.95). Interventions were significantly associated with tobacco abstinence for both people in treatment (RR 1.99, 95% CI 1.59 to 2.50) and people in recovery (RR 1.33, 95% CI 1.06 to 1.67), and for people with alcohol dependence (RR 1.47, 95% CI 1.20 to 1.81) and people with other drug dependencies (RR 1.85, 95% CI 1.43 to 2.40). Offering tobacco cessation therapy to people in treatment or recovery for other drug dependence was not associated with a difference in abstinence rates from alcohol and other drugs (RR 0.97, 95% CI 0.91 to 1.03, 11 studies, 2231 participants, moderate evidence of heterogeneity (I2 = 66%)). Data on adverse effect of the interventions were limited. The studies included in this review suggest that providing tobacco cessation interventions targeted to smokers in treatment and recovery for alcohol and other drug dependencies increases tobacco abstinence. There was no evidence that providing interventions for tobacco cessation affected abstinence from alcohol and other drugs. The association between tobacco cessation interventions and tobacco abstinence was consistent for both pharmacotherapy and combined counselling and pharmacotherapy, for participants both in treatment and in recovery, and for people with alcohol dependency or other drug dependency. The evidence for the interventions was low quality due primarily to incomplete reporting of the risks of bias and clinical heterogeneity in the nature of treatment. Certain results were sensitive to the length of follow-up or the type of pharmacotherapy, suggesting that further research is warranted regarding whether tobacco cessation interventions are associated with tobacco abstinence for people in recovery, and the outcomes associated with NRT versus non-NRT or combined pharmacotherapy. Overall, the results suggest that tobacco cessation interventions incorporating pharmacotherapy should be incorporated into clinical practice to reduce tobacco addiction among people in treatment for or recovery from alcohol and other drug dependence.\n",
      "We looked for studies that enrolled adult smokers who were either in treatment or had completed treatment for substance abuse, in hospital, outpatient or community settings and randomised them to either a treatment to help them stop smoking or a control. We last searched for evidence in August 2016. We found 34 published studies. The types of smoking cessation treatment tested included: counselling (which might be a brief advice session or multiple sessions of behavioural support, either individually or in a group); medicine (called pharmacotherapy; including any type of nicotine replacement therapy, with or without other medicines that help smokers to stop smoking); or a combination of counselling and pharmacotherapy. We combined the results of trials separately for each of these types of treatment, although different trials used different treatments. People who were in the control groups received usual care, brief advice about quitting smoking, or were put on a waiting list to receive treatment later. Most trials assessed the number of people who had quit smoking at least six months after beginning treatment although we also included some studies with a shorter time. Eleven studies with 1808 people tested the effects of various types of pharmacotherapy. There was evidence that people given pharmacotherapy were more successful at quitting smoking. Twelve studies with 2229 participants tested treatments that combined pharmacotherapy and counselling. There was evidence that people given combined treatments were more successful at quitting smoking. Eleven studies with 1759 people tested the effect of counselling compared to usual care. Combining these results did not show evidence of a benefit of counselling alone. Eleven studies with 2231 people reported whether people remained abstinent from alcohol and other drugs. Providing tobacco cessation interventions did not make people more likely to return to using alcohol or other drugs. We found no evidence that it made a difference whether people were given treatment to quit smoking when they were just starting treatment for other drug use or after they were in recovery. Results were also similar for people who were treated for alcohol use and for people who were treated for other drugs such as heroin. We judged the quality of the evidence to be low. Many studies did not give enough details about the methods that they used. The studies also considered very different types of treatment, making comparisons challenging.\n",
      "\n",
      "\n",
      "Idx 83\n",
      "Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs. There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.\n",
      "This review of trials found only four studies which had an overall low quality. Three trials showed no significant differences between momordica charantia and placebo or antidiabetic drugs (glibenclamide and metformin) in the blood sugar response. The duration of treatment ranged from four weeks to three months, and altogether 479 patients with type 2 diabetes mellitus participated. No trial investigated death from any cause, morbidity, health-related quality of life or costs. Adverse effects were mostly moderate, including diarrhoea and abdominal pain. However, reporting of adverse effects was incomplete in the included studies. There are many varieties of preparations of momordica charantia, as well as variations in its use as a vegetable. Further studies are needed to assess the quality of the various momordica charantia preparations as well as to further evaluate its use in the diet of diabetic people.\n",
      "\n",
      "\n",
      "Idx 84\n",
      "We included five RCTs with 666 randomized adults. We identified three ongoing studies. All study participants were scheduled for elective general surgery (including abdominal, urological, orthopaedic and gynaecological surgery) under general, spinal or regional anaesthesia. Studies compared continuation of single or dual antiplatelet therapy (aspirin or clopidogrel) with discontinuation of therapy for at least five days before surgery. Three studies reported adequate methods of randomization, and two reported methods to conceal allocation. Three studies were placebo-controlled trials and were at low risk of performance bias, and three studies reported adequate methods to blind outcome assessors to group allocation. Attrition was limited in four studies and two studies had reported prospective registration with clinical trial registers and were at low risk of selective outcome reporting bias. We reported mortality at two time points: the longest follow-up reported by study authors up to six months, and time point reported by study authors up to 30 days. Five studies reported mortality up to six months (of which four studies had a longest follow-up at 30 days, and one study at 90 days) and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality up to six months (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.34 to 4.27; 659 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from eight fewer to 40 more). Combining the four studies with a longest follow-up at 30 days alone showed the same effect estimate, and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality at 30 days after surgery (RR 1.21, 95% CI 0.34 to 4.27; 616 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from nine fewer to 42 more). We found that either continuation or discontinuation of antiplatelet therapy probably makes little or no difference in incidences of blood loss requiring transfusion (RR 1.37, 95% CI 0.83 to 2.26; 368 participants; absolute effect of 42 more participants per 1000 requiring transfusion in the continuation group, ranging from 19 fewer to 119 more; four studies; moderate-certainty evidence); and may make little or no difference in incidences of blood loss requiring additional surgery (RR 1.54, 95% CI 0.31 to 7.58; 368 participants; absolute effect of six more participants per 1000 requiring additional surgery in the continuation group, ranging from seven fewer to 71 more; four studies; low-certainty evidence). We found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to incidences of ischaemic events (to include peripheral ischaemia, cerebral infarction, and myocardial infarction) within 30 days of surgery (RR 0.67, 95% CI 0.25 to 1.77; 616 participants; absolute effect of 17 fewer participants per 1000 with an ischaemic event in the continuation group, ranging from 39 fewer to 40 more; four studies; low-certainty evidence). We used the GRADE approach to downgrade evidence for all outcomes owing to limited evidence from few studies. We noted a wide confidence in effect estimates for mortality at the end of follow-up and at 30 days, and for blood loss requiring transfusion which suggested imprecision. We noted visual differences in study results for ischaemic events which suggested inconsistency. We found low-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery may make little or no difference to mortality, bleeding requiring surgical intervention, or ischaemic events. We found moderate-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery probably makes little or no difference to bleeding requiring transfusion. Evidence was limited to few studies with few participants, and with few events. The three ongoing studies may alter the conclusions of the review once published and assessed.\n",
      "The evidence from randomized controlled trials is current to January 2018. We included five trials with 666 adults in the review. Three studies are ongoing. All participants were taking antiplatelet therapy (aspirin or clopidogrel) at the start of the study. Two studies stopped antiplatelet drugs for at least five days before surgery, and three studies gave participants a placebo instead of antiplatelet therapy during this time. We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to the number of people who died up to 30 days or six months after surgery (five studies, 659 participants). We found moderate-certainty evidence that either continuing or stopping antiplatelet therapy probably makes little or no difference to incidences of bleeding serious enough to need a blood transfusion during or immediately after surgery (four studies, 368 participants). We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to bleeding serious enough to need further surgery (four studies, 368 participants), and may make little or no difference to the number of ischaemic events such as stroke or heart attack (four studies, 616 participants). Some studies had low risk of bias because they had clearly reported their methods for randomizing people to each group, and three studies used a placebo agent so that people did not know whether or not they were continuing their usual antiplatelet therapy. However, we found few studies with few events, with wide variation in results. To continue or stop taking antiplatelet drugs for a few days before non-cardiac surgery might make little or no difference to the number of people who died, who had bleeding that needed further surgery or who had ischaemic events, and it probably makes little or no difference to bleeding that needed a blood transfusion. We found three ongoing studies which will increase certainty in the effect in future updates of the review.\n",
      "\n",
      "\n",
      "Idx 85\n",
      "We included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry. Home fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 μg/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI −0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity. In comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD −2.81 g/L, 95% CI −10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously. Reporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce. It appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. Home fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.\n",
      "We searched up to July 2019 for all studies that assessed the use of MNP for improving the health and nutrition of children under two years of age. We included 29 studies that involved 33,147 infants and young children from low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean. Twenty-six studies with 27,051 children contributed data. Of these 26 studies, 24 compared the use of MNP versus no intervention or placebo, and 2 compared the use of MNP versus an iron-only supplement (iron drops) given daily. We found that a variety of MNP formulations containing between 5 and 22 vitamins and minerals were given for 2 to 44 months to infants and young children aged 6 to 23 months. Most studies were funded by government programmes or foundations; only 2 were funded by industry. The use of MNP containing at least iron, zinc, and vitamin A for home fortification of foods was associated with reduced risk of anaemia of 18% and iron deficiency of 53% in children aged six months to two years compared with no intervention. Also, haemoglobin concentration and iron status improved. Studies did not find any effects on growth. There was no additional benefit in reducing risk of anaemia and improving haemoglobin concentration compared to usually recommended iron drops or syrups; however, only two studies compared these different interventions. No trials reported death attributable to the intervention. Information on deaths, side effects, and morbidity, including malaria and diarrhoea, was scarce. The use of MNP was beneficial for young children 6 to 23 months of age, independent of whether they lived in settings with different anaemia and malaria backgrounds and regardless of the length of the intervention. MNP is better than no intervention or placebo and may be comparable to daily iron supplementation.The benefits of this intervention as a child survival strategy or for developmental outcomes are still unclear, and further investigation is required. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. For the comparison of MNP versus no intervention or placebo, we judged the certainty of evidence to be moderate for anaemia and high for iron deficiency. The certainty of evidence for all other outcomes in this comparison was either low or moderate. Two trials that compared the use of MNP versus iron supplement showed similar effects on anaemia and haemoglobin but less diarrhoea; however, we judged the certainty of evidence as low for anaemia and very low for haemoglobin concentration due to the small number of study participants.\n",
      "\n",
      "\n",
      "Idx 86\n",
      "Nine trials including more than 25,000 participants were included in this review. No effect was observed on child health, measures of child mental health or emotional state. Non-significant effects favouring the intervention group were seen for child cognitive development and educational achievement, and a non-significant effect favouring controls in rates of teenage pregnancy. The review set out to examine the potential of financial support to poor families to improve circumstances for children. However, on the basis of current evidence we cannot state unequivocally whether financial benefits delivered as an intervention are effective at improving child health or well-being in the short term. Our conclusions are limited by the fact that most of the studies had small effects on total household income and that, while no conditions were attached to how money was spent, all studies included strict conditions for receipt of payments. We note particular concerns by some authors that sanctions and conditions (such as working hours) placed on families may increase family stress.\n",
      "This review aimed to assess whether additional monies provided to socially or economically disadvantaged families could affect children's health, well-being and educational attainment. Nine studies were identified that met inclusion criteria. There was tentative evidence of benefit in early language development, but given lack of effect on all other outcomes, authors conclude that the evidence did not show an effect on child outcomes in the short to medium term in response to direct financial benefits to families. In the context of the monetary value of interventions observed, and the conditions placed on receipt of benefits, authors conclude this is a statement of \"no evidence of effect\" rather than \"evidence of no effect\". Implications for research and practice are noted.\n",
      "\n",
      "\n",
      "Idx 87\n",
      "Overall, 10 RCTs with 565 participants which investigated different non-pharmacological interventions for the management of chronic pain in MS fulfilled the review inclusion criteria. The non-pharmacological interventions evaluated included: transcutaneous electrical nerve stimulation (TENS), psychotherapy (telephone self-management, hypnosis and electroencephalogram (EEG) biofeedback), transcranial random noise stimulation (tRNS), transcranial direct stimulation (tDCS), hydrotherapy (Ai Chi) and reflexology. There is very low-level evidence for the use of non-pharmacological interventions for chronic pain such as TENS, Ai Chi, tDCS, tRNS, telephone-delivered self-management program, EEG biofeedback and reflexology in pain intensity in pwMS. Although there were improved changes in pain scores and secondary outcomes (such as fatigue, psychological symptoms, spasm in some interventions), these were limited by methodological biases within the studies. Despite the use of a wide range of non-pharmacological interventions for the treatment of chronic pain in pwMS, the evidence for these interventions is still limited or insufficient, or both. More studies with robust methodology and greater numbers of participants are needed to justify the effect of these interventions for the management of chronic pain in pwMS.\n",
      "Overall, we found 10 studies evaluating different non-medication treatments to treat chronic pain in persons with MS. The treatments evaluated included: transcutaneous electrical nerve stimulation, transcranial direct stimulation, transcranial random noise stimulation, reflexology, psychotherapy and hydrotherapy. These studies included 565 participants and used a range of different methods to measure pain and other outcomes. Comparison groups also varied. Results from these studies show a very low level of evidence for the use of any non-medication treatments for chronic pain in persons with MS. We assessed the overall quality of the studies as very low, as many studies included only small numbers of participants and had other methodological issues. More research with good methodological quality and greater number of participants are needed to determine the effectiveness of such treatments.\n",
      "\n",
      "\n",
      "Idx 88\n",
      "We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis. Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi. Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews. There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life. The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.\n",
      "In January 2016, we identified 21 Cochrane Reviews which covered 10 different diagnoses (osteoarthritis (a joint disease), rheumatoid arthritis (joint pain and swelling), fibromyalgia (widespread pain condition), low back pain, intermittent claudication (cramping pain in the legs), dysmenorrhoea (period pain), mechanical neck disorders (neck pain), spinal cord injury, postpolio syndrome (a condition occurring in people who have had polio), patellofemoral pain (pain at the front of the knee)). The physical activity or exercise programme used in the trials ranged in frequency, intensity, and type, including land- and water-based activities, those focusing on building strength, endurance, flexibility and range of motion, and muscle activation exercises. The quality of the evidence was low. This was mostly due to the small numbers of people with chronic pain who participated in each reviewed study. Ideally, a study should have hundreds of people assigned to each group, whereas most of the studies included in the review process here had fewer than 50 people in total. There was evidence that physical activity reduced the severity of pain, improved physical function, and had a variable effect on both psychological function and quality of life. However, these results were not found in all studies. The inconsistency could be due to the quality of the studies or because of the mix of different types of physical activity tested in the studies. Additionally, participants had predominantly mild-to-moderate pain, not moderate-to-severe pain. According to the available evidence (only 25% of included studies reported on possible harm or injury from the intervention), physical activity did not cause harm. Muscle soreness that sometimes occurs with starting a new exercise subsided as the participants adapted to the new activities. This is important as it shows physical activity in general is acceptable and unlikely to cause harm in people with chronic pain, many of whom may have previously feared it would increase their pain further. Future studies should focus on increasing participant numbers, including a wider range of severity of pain (more people with more severe pain), and lengthening both the intervention (exercise programme) itself, and the follow-up period. This pain is chronic in nature, and so a long-term intervention, with longer periods of recovery or follow-up, may be more effective.\n",
      "\n",
      "\n",
      "Idx 89\n",
      "We included 12 studies involving 2887 participants with LBP. Three studies had low risk of bias. Included studies evaluated a range of chiropractic procedures in a variety of sub-populations of people with LBP. No trials were located of combined chiropractic interventions compared to no treatment. For acute and subacute LBP, chiropractic interventions improved short- and medium-term pain (SMD -0.25 (95% CI -0.46 to -0.04) and MD -0.89 (95%CI -1.60 to -0.18)) compared to other treatments, but there was no significant difference in long-term pain (MD -0.46 (95% CI -1.18 to 0.26)). Short-term improvement in disability was greater in the chiropractic group compared to other therapies (SMD -0.36 (95% CI -0.70 to -0.02)). However, the effect was small and all studies contributing to these results had high risk of bias. There was no difference in medium- and long-term disability. No difference was demonstrated for combined chiropractic interventions for chronic LBP and for studies that had a mixed population of LBP. Combined chiropractic interventions slightly improved pain and disability in the short-term and pain in the medium-term for acute and subacute LBP. However, there is currently no evidence that supports or refutes that these interventions provide a clinically meaningful difference for pain or disability in people with LBP when compared to other interventions. Future research is very likely to change the estimate of effect and our confidence in the results.\n",
      "The review shows that while combined chiropractic interventions slightly improved pain and disability in the short term and pain in the medium term for acute and subacute low-back pain, there is currently no evidence to support or refute that combined chiropractic interventions provide a clinically meaningful advantage over other treatments for pain or disability in people with low-back pain. Any demonstrated differences were small and were only seen in studies with a high risk of bias. Future research is very likely to change the results and our confidence in them. Well conducted randomised trials are required that compare combined chiropractic interventions to other established therapies for low-back pain.\n",
      "\n",
      "\n",
      "Idx 90\n",
      "We included three trials involving 254 adolescent girls with type 1 or type 2 diabetes, with an overall unclear to high risk of bias. The three trials were conducted at diabetes clinics in the USA, and assessed the READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls) programme versus standard care. Considering primary outcomes, one trial reported no pregnancies in the trial period (12 months) (very low-quality evidence, with downgrading based on study limitations (risk of bias) and imprecision); in the other two trials, pregnancy was an exclusion criterion, or was not clearly reported on. None of the trials reported on the other primary maternal outcomes, hypertensive disorders of pregnancy and caesarean section; or primary infant outcomes, large-for-gestational age, perinatal mortality, death or morbidity composite, or congenital malformations. Similarly, none of the trials reported on the secondary outcomes, for which we had planned to assess the quality of the evidence using the GRADE approach (maternal: induction of labour; perineal trauma; gestational weight gain; long-term cardiovascular health; infant: adiposity; type 1 or 2 diabetes; neurosensory disability). The majority of secondary maternal and infant outcomes, and outcomes relating to the use and costs of health services were not reported by the three included trials. Regarding behaviour changes associated with the intervention, in one trial, participants in the preconception care group had a slightly higher score for the actual initiation of discussion regarding preconception care with healthcare providers at follow-up (nine months), compared with those in the standard care group (mean difference 0.40, 95% confidence interval -0.02 to 0.82 (on a scale of 0 to 4 points); participants = 87) (a summation of four dichotomous items; possible range 0 to 4, with 0 being no discussion). There are insufficient RCT data available to assess the effects of preconception care for diabetic women on health outcomes for mothers and their infants. More high-quality evidence is needed to determine the effects of different protocols of preconception care for diabetic women. Future trials should be powered to evaluate effects on short- and long-term maternal and infant outcomes, and outcomes relating to the use and costs of health services. We have identified three ongoing studies that we will consider in the next review update.\n",
      "We found three randomised controlled trials, conducted at diabetes clinics in the USA. The total number of participants in the studies was 254. The participants were all adolescent girls involved in the programme READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls). Their care was compared with standard care. None of these three trials gave us the information on the health outcomes we needed. In one trial, there were no pregnancies among the participants during the period of the study, and the other two trials’ reporting of pregnancy was not sufficient. There were no data about short and long term outcomes for the mothers and their babies, or about the use of the health service and related costs. Because the information is lacking, we have no evidence from this Cochrane review to guide practice on this topic. Further large, well-designed, randomised controlled trials are required. Three trials are ongoing and will be considered in the next update of this review.\n",
      "\n",
      "\n",
      "Idx 91\n",
      "We included one RCT, two quasi-RCTs and 10 cohort studies (3925 participants). No studies were rated as low risk of bias for all criteria. Critical appraisal was constrained by a lack of information in most studies. The overall quality of the evidence was moderate. Seven studies (1432 participants) assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity was explained by subgrouping according to the blood product used as an approximation of dose of immunoglobulin. When given within seven days of exposure, immunoglobulins were effective at preventing measles: gamma globulin (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of different blood products were supported by studies not included in the meta-analysis and by two studies (702 participants) that found gamma globulin more effective than serum (RR 0.56, 95% CI 0.46 to 0.69). Based on three studies (893 participants) immunoglobulin was effective at preventing death due to measles compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44). Two studies included measles vaccine alone among the intervention groups. Meta-analysis could not be undertaken. Both studies suggested the vaccine was more effective than gamma globulin. No serious adverse events were observed in any of the included studies, although reporting of adverse events was poor overall. Non-serious adverse events included transient fever, rash, muscle stiffness, local redness and induration. Passive immunisation within seven days of exposure is effective at preventing measles, with the risk for non-immune people up to 83% less than if no treatment is given. Given an attack rate of 45 per 1000 (per the control group of the most recent included study), gamma globulin compared to no treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the attack rate of the other included study assessing gamma globulin), the ARR of gamma globulin compared to no treatment is 629 and the NNTB is two. It seems the dose of immunoglobulin administered impacts on effectiveness. A minimum effective dose of measles-specific antibodies could not be identified. Passive immunisation is effective at preventing deaths from measles, reducing the risk by 76% compared to no treatment. Whether the benefits of passive immunisation vary among subgroups of non-immune exposed people could not be determined. Due to a paucity of evidence comparing vaccine to passive immunisation, no firm conclusions can be drawn regarding relative effectiveness. The included studies were not specifically designed to detect adverse events. Future research should consider the effectiveness of passive immunisation for preventing measles in high-risk populations such as pregnant women, immunocompromised people and infants. Further efforts should be made to determine the minimum effective dose of measles-specific antibodies for post-exposure prophylaxis and the relative effectiveness of vaccine compared to immunoglobulin.\n",
      "Based on seven studies (1432 people), of overall moderate quality, injecting antibodies into a muscle of people who came into contact with measles, but lacked their own antibodies, was effective at preventing them catching the disease compared to those who received no treatment. Using the modern day antibody preparation, people were 83% less likely to develop measles than those who were not treated. It was very effective at preventing them developing complications if they did contract measles and very effective at preventing death. The included studies generally did not intend to measure possible harms from the injections. Minor side effects were reported, such as muscle stiffness, redness around the injection site, fever and rash. Importantly, only two studies compared the measles vaccine with the antibody injection in this group of people, so no firm conclusions could be drawn about the relative effectiveness of these interventions. The antibody injection is often recommended for pregnant women, infants and immunocompromised people (if they do not have their own antibodies to measles and come into contact with someone who is contagious with measles). The included studies did not include these groups of people, so it is unknown whether the effectiveness of antibody injections is different for them. We were also unable to identify the minimum dose of antibodies required as only one study measured the specific amount of measles antibodies in the injections and one other study estimated this figure; the results of these two studies were not consistent. The evidence is current to August 2013.\n",
      "\n",
      "\n",
      "Idx 92\n",
      "We included 37 RCTs (3872 women), one ongoing trial, and one trial awaiting classification. These trials made nine different comparisons between protocols. Twenty of the RCTs compared long protocols and short protocols. Only 19/37 RCTs reported live birth or ongoing pregnancy. There was no conclusive evidence of a difference between a long protocol and a short protocol in live birth and ongoing pregnancy rates (OR 1.30, 95% CI 0.94 to 1.81; 12 RCTs, n = 976 women, I² = 15%, low quality evidence). Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. There was evidence of an increase in clinical pregnancy rates (OR 1.50, 95% CI 1.18 to 1.92; 20 RCTs, n = 1643 women, I² = 27%, moderate quality evidence) associated with the use of a long protocol. There was no evidence of a difference between the groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort protocol (OR 1.78, 95% CI 0.72 to 4.36; one RCT, n = 150 women, low quality evidence), long luteal versus long follicular phase protocol (OR 1.89, 95% CI 0.87 to 4.10; one RCT, n = 223 women, low quality evidence), when GnRHa was stopped versus when it was continued (OR 0.75, 95% CI 0.42 to 1.33; three RCTs, n = 290 women, I² = 0%, low quality evidence), when the dose of GnRHa was reduced versus when the same dose was continued (OR 1.02, 95% CI 0.68 to 1.52; four RCTs, n = 407 women, I² = 0%, low quality evidence), when GnRHa was discontinued versus continued after human chorionic gonadotrophin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; one RCT, n = 181 women, low quality evidence), and when administration of GnRHa lasted for two versus three weeks before stimulation (OR 1.14, 95% CI 0.49 to 2.68; one RCT, n = 85 women, low quality evidence). Our primary outcomes were not reported for any other comparisons. Regarding adverse events, there were insufficient data to enable us to reach any conclusions except about the cycle cancellation rate. There was no conclusive evidence of a difference in cycle cancellation rate (OR 0.95, 95% CI 0.59 to 1.55; 11 RCTs, n = 1026 women, I² = 42%, low quality evidence) when a long protocol was compared with a short protocol. This suggests that in a population in which 9% of women would have their cycles cancelled using a short protocol, between 5.5% and 14% will have cancelled cycles when using a long protocol. The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years. When long GnRHa protocols and short GnRHa protocols were compared, we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates, but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects.\n",
      "We found 37 randomised controlled trials (RCTs) of 3872 women comparing the use of GnRHa in various protocols. Twenty of these RCTs (1643 women) compared a long protocol with a short protocol. The evidence is current to April 2015. In comparisons of long GnRHa protocols (where GnRHa is given for at least 14 days prior to the start of ovarian stimulation) versus short GnRHa protocols (when the GnRHa is given at the start of stimulation) there was no conclusive evidence of a difference in live birth and ongoing pregnancy rates. However there was moderate quality evidence of higher clinical pregnancy rates in the long protocol groups. Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects. Further research is needed to determine which long protocol is most cost effective and acceptable to women. The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years.\n",
      "\n",
      "\n",
      "Idx 93\n",
      "Twelve trials including 754 participants met our inclusion criteria. Trials were from eight to 26 weeks in duration. We judged all trials to be at moderate or high risk of bias in at least some domains. Reporting of some risk of bias domains was poor. Our analyses comparing aerobic exercise to any active intervention showed no evidence of benefit from aerobic exercise in any cognitive domain. This was also true of our analyses comparing aerobic exercise to no intervention. Analysing only the subgroup of trials in which cardiorespiratory fitness improved in the aerobic exercise group showed that this improvement did not coincide with improvements in any cognitive domains assessed. Our subgroup analyses of aerobic exercise versus flexibility or balance interventions also showed no benefit of aerobic exercise in any cognitive domain. Dropout rates did not differ between aerobic exercise and control groups. No trial reported on adverse effects. Overall none of our analyses showed a cognitive benefit from aerobic exercise even when the intervention was shown to lead to improved cardiorespiratory fitness. We found no evidence in the available data from RCTs that aerobic physical activities, including those which successfully improve cardiorespiratory fitness, have any cognitive benefit in cognitively healthy older adults. Larger studies examining possible moderators are needed to confirm whether or not aerobic training improves cognition.\n",
      "In this Cochrane Review, 12 trials including 754 participants met our inclusion criteria. Eight of the 12 trials reported that the aerobic exercise interventions resulted in increased fitness of the trained group. However, when we combined results across the trials, we did not find any significant benefits of aerobic exercise or increased fitness on any aspect of cognition. Many included trials had problems with their methods or reporting which reduced our confidence in the findings. We did not find evidence that aerobic exercise or increased fitness improves cognitive function in older people. However, it remains possible that it may be helpful for particular subgroups of people, or that more intense exercise programmes could be beneficial. Therefore further research in this area is necessary.\n",
      "\n",
      "\n",
      "Idx 94\n",
      "In this review, we included 37 trials involving 15,813 children and adolescents. All trials tested supervised use of fluoride mouthrinse in schools, with two studies also including home use. Almost all children received a fluoride rinse formulated with sodium fluoride (NaF), mostly on either a daily or weekly/fortnightly basis and at two main strengths, 230 or 900 ppm F, respectively. Most studies (28) were at high risk of bias, and nine were at unclear risk of bias. From the 35 trials (15,305 participants) that contributed data on permanent tooth surface for meta-analysis, the D(M)FS pooled PF was 27% (95% confidence interval (CI), 23% to 30%; I2 = 42%) (moderate quality evidence). We found no significant association between estimates of D(M)FS prevented fractions and baseline caries severity, background exposure to fluorides, rinsing frequency or fluoride concentration in metaregression analyses. A funnel plot of the 35 studies in the D(M)FS PF meta-analysis indicated no relationship between prevented fraction and study precision (no evidence of reporting bias). The pooled estimate of D(M)FT PF was 23% (95% CI, 18% to 29%; I² = 54%), from the 13 trials that contributed data for the permanent teeth meta-analysis (moderate quality evidence). We found limited information concerning possible adverse effects or acceptability of the treatment regimen in the included trials. Three trials incompletely reported data on tooth staining, and one trial incompletely reported information on mucosal irritation/allergic reaction. None of the trials reported on acute adverse symptoms during treatment. This review found that supervised regular use of fluoride mouthrinse by children and adolescents is associated with a large reduction in caries increment in permanent teeth. We are moderately certain of the size of the effect. Most of the evidence evaluated use of fluoride mouthrinse supervised in a school setting, but the findings may be applicable to children in other settings with supervised or unsupervised rinsing, although the size of the caries-preventive effect is less clear. Any future research on fluoride mouthrinses should focus on head-to-head comparisons between different fluoride rinse features or fluoride rinses against other preventive strategies, and should evaluate adverse effects and acceptability.\n",
      "We included 37 studies in which more than 15,000 children (aged six to 14 years) were treated with fluoride mouthrinse or placebo (a mouthrinse with no active ingredient) or received no treatment. All studies assessed supervised use of fluoride mouthrinse in school settings, with two studies also including home use. Most children received a sodium fluoride (NaF) solution, given at 230 parts per million of fluoride (ppm F) daily or a higher concentration of 900 ppm F weekly or fortnightly. Studies lasted from two to three years. Reports were published between 1965 and 2005, and studies took place in several countries. This review update confirmed that supervised regular use of fluoride mouthrinse can reduce tooth decay in children and adolescents. Combined results of 35 trials showed that, on average, there is a 27% reduction in decayed, missing and filled tooth surfaces in permanent teeth with fluoride mouthrinse compared with placebo or no mouthrinse. This benefit is likely to be present even if children use fluoride toothpaste or live in water-fluoridated areas. Combined results of 13 trials found an average 23% reduction in decayed, missing and filled teeth (rather than tooth surfaces) in permanent teeth with fluoride mouthrinse compared with placebo or no mouthrinse. No trials have looked at the effect of fluoride rinse on baby teeth. We found little information about unwanted side effects or about how well children were able to cope with the use of mouthrinses. Regular use of fluoride mouthrinse under supervision results in a large reduction in tooth decay in children's permanent teeth. We found little information about potential adverse effects and acceptability. Available evidence for permanent teeth is of moderate quality. This means we are moderately confident in the size of the effect. Very little evidence is available to assess adverse effects.\n",
      "\n",
      "\n",
      "Idx 95\n",
      "Six studies were eligible for inclusion (517 patients). Five studies compared type I IFNs to placebo injections (485 patients) and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis (32 patients). The active comparator study was rated as high risk of bias due to an open-label design. Three studies were rated as unclear risk of bias for random sequence generation and allocation concealment. Two studies described as double blind were rated as unclear risk of bias for blinding. There was no significant benefit of type I IFNs over placebo for inducing clinical remission or improvement in patients with active ulcerative colitis. Thirty-six per cent (87/242) of patients in the type I IFNs group achieved clinical remission by 8 to 12 weeks compared to 30% (36/120) of placebo patients (RR 1.16, 95% CI 0.84 to 1.58; 4 studies, 362 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical remission was moderate due to sparse data (123 events). Fifty-six per cent (149/264) of patients in the type I IFNs group improved clinically by 8 to 12 weeks compared to 48% (77/161) of placebo patients (RR 1.16, 95% CI 0.96 to 1.40; 4 studies, 425 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical improvement was moderate due to sparse data (226 events). Patients who received type I IFNs were significantly more likely to withdraw from the studies due to adverse events than those who received placebo. Seven per cent (18/42) of type I IFNs patients withdrew due to adverse events compared to 2% (3/152) of placebo patients (RR 3.16, 95% CI 1.06 to 9.40). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome withdrawal due to adverse events was low due to very sparse data (21 events). The study comparing type I IFNs to prednisolone enemas found no difference between the treatment groups in quality of life or disease activity scores. Common adverse events included headaches, arthralgias, myalgias, fatigue, back pain, nausea, application site reactions, rigors, and fevers. There were no statistically significant differences in the other secondary outcomes. Moderate quality evidence suggests that type I IFNs are not effective for the induction of remission in UC. In addition, there are concerns regarding the tolerability of this class of treatment.\n",
      "The researchers identified six studies that included a total of 517 participants. Five studies (total 485 participants) compared type I IFNs to placebo (fake medicine) injections. One small (32 participants) low quality study compared types I IFNs to prednisolone (a steroid drug) enemas. This study did not measure remission and found no difference between the treatment groups in quality of life or disease activity scores. There was no difference between type I interferons and placebo treatment groups for the number of people who achieved remission or improvement of their symptoms. These results suggest that type I IFNs do not produce remission from ulcerative colitis. Common side effects included headaches, arthralgias (joint pain), myalgias (muscle pain), fatigue, back pain, nausea, injection site reactions, rigors (cold and shivering), and fevers. At present, the results from medical trials do not support the use of type I IFNs for the production of remission in active ulcerative colitis.\n",
      "\n",
      "\n",
      "Idx 96\n",
      "For the first publication of this review, two RCTs involving 260 children with measles which compared vitamin A with placebo met the inclusion criteria. Neither study reported blindness or other ocular morbidities as end points. One trial of moderate quality suggested evidence of a significant increase in serum retinol levels in the vitamin A group one week after two doses of vitamin A (MD 9.45 µg/dL, 95% CI 2.19 to 16.71; 17 participants, moderate-quality evidence), but not six weeks after three doses of vitamin A (MD 2.56 µg/dL, 95% CI -5.28 to 10.40; 39 participants, moderate-quality evidence). There was no significant difference in weight gain six weeks (MD 0.39 kg, -0.04 to 0.82; 48 participants, moderate-quality evidence) and six months (MD 0.52 kg, 95% CI -0.08 to 1.12; 36 participants, moderate-quality evidence) after three doses of vitamin A. The second trial found no significant difference in serum retinol levels two weeks after a single dose of vitamin A (MD 2.67 µg/dL, 95% CI -0.29 to 5.63; 155 participants, moderate-quality evidence). Percentage of undernutrition between the two groups did not differ significantly at one week (RR 0.93, 95% CI 0.56 to 1.54, 145 participants) and two weeks (RR 0.82, 95% CI 0.52 to 1.29, 147 participants) after a single dose of vitamin A. No adverse event was reported in either study. We did not find any new RCTS for this second update. We did not find any trials assessing whether or not vitamin A supplementation in children with measles prevents blindness, as neither study reported blindness or other ocular morbidities as end points.\n",
      "We included two randomised controlled trials of moderate quality, including 260 children with measles, comparing children given vitamin A with children not given vitamin A. The evidence is current to December 2015. Two doses of vitamin A given on two consecutive days to hospitalised children with measles led to an increase in the blood concentration of vitamin A after one week. However, there is a limitation in that neither of the two included studies reported blindness or other eye problems in children infected with measles. Also, no side effects of the treatment were reported in the included studies. We do not have sufficient evidence to demonstrate the benefit or otherwise of vitamin A in the prevention of blindness in children infected with measles. The quality of the evidence and methodology of both studies was moderate. The sample size of the included studies was relatively small, which could affect the accuracy of the results.\n",
      "\n",
      "\n",
      "Idx 97\n",
      "We identified 10 studies (total of 298 children; we identified two studies for this update) including two randomised controlled trials (RCTs) that assessed adrenal function. None of the included studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. Owing to substantial differences between studies, we could not pool results. All studies had risk of bias issues. Included studies demonstrated that adrenal insufficiency occurs in nearly all children during the first days after cessation of glucocorticoid treatment for childhood ALL. Most children recovered within a few weeks, but a small number of children had ongoing adrenal insufficiency lasting up to 34 weeks. Included studies evaluated several risk factors for (prolonged) adrenal insufficiency. First, three studies including two RCTs investigated the difference between prednisone and dexamethasone in terms of occurrence and duration of adrenal insufficiency. The RCTs found no differences between prednisone and dexamethasone arms. In the other (observational) study, children who received prednisone recovered earlier than children who received dexamethasone. Second, treatment with fluconazole appeared to prolong the duration of adrenal insufficiency, which was evaluated in two studies. One of these studies reported that the effect was present only when children received fluconazole at a dose higher than 10 mg/kg/d. Finally, two studies evaluated the presence of infection, stress episodes, or both, as a risk factor for adrenal insufficiency. In one of these studies (an RCT), trial authors found no relationship between the presence of infection/stress and adrenal insufficiency. The other study found that increased infection was associated with prolonged duration of adrenal insufficiency. We concluded that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. No data were available on the levels of the hypothalamus and the pituitary; therefore, we could draw no conclusions regarding these outcomes. Clinicians may consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL to reduce the risk of life-threatening complications. However, additional high-quality research is needed to inform evidence-based guidelines for glucocorticoid replacement therapy. Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as these treatments may prolong the duration of adrenal insufficiency, especially when administered at a dose higher than 10 mg/kg/d. Finally, it would be relevant to investigate further the relationship between present infection/stress and adrenal insufficiency in a larger, separate study specially designed for this purpose.\n",
      "This systematic review included eight cohort studies and two randomised studies with a total number of 298 patients. All studies assessed adrenal function in paediatric patients treated with glucocorticoids for ALL. The evidence is current to December 2016. None of these studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. We could not combine the results of different studies because of heterogeneity. Adrenal insufficiency occurred in nearly all children during the first days after completion of glucocorticoid therapy. Most children recovered within a few weeks, but a small number had ongoing adrenal insufficiency lasting up to 34 weeks. Three studies looked into differences in duration of adrenal insufficiency between children who received prednisone and those who were given dexamethasone (two types of glucocorticoids). Two of these three studies found no differences. In the other study, children who received prednisone recovered earlier than those who received dexamethasone. Also, treatment with a certain antifungal drug (fluconazole) seemed to prolong the duration of adrenal insufficiency. Two studies investigated this. Finally, two studies evaluated the presence of infection/stress as a risk factor for adrenal insufficiency. One study found no relationship. The other study reported that increased infection was associated with a longer duration of adrenal insufficiency. More high-quality research is needed to define the exact occurrence and duration of HPA axis suppression. Then adequate guidelines for glucocorticoid replacement therapy can be formulated. All of the included studies had some risk of bias issues.\n",
      "\n",
      "\n",
      "Idx 98\n",
      "Twenty randomized trials were identified of which thirteen were included in the quantitative analysis with data from 1022 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), sulfasalazine, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was insufficient data to examine toxicity. Parenteral high dose methotrexate and sulfasalazine are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.\n",
      "The objective was to assess the benefits of the treatment [sulfasalazine, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, methotrexate] for psoriatic arthritis and to assess the side effects. Parenteral methotrexate and sulfasalazine resulted in important benefit in over half the patients for psoriatic arthritis in these studies. There was insufficient data to evaluate other therapies and to examine toxicity. Further multicentre trials are required to establish the efficacy of azathioprine, oral methotrexate, etretinate, and colchicine.\n",
      "\n",
      "\n",
      "Idx 99\n",
      "Five trials with a total of 1159 women were included. All used X-ray pelvimetry to assess the pelvis. X-ray pelvimetry versus no pelvimetry or clinical pelvimetry is the only comparison included in this review due to the lack of trials identified that examined other types of radiological pelvimetry or that compared clinical pelvimetry versus no pelvimetry. The included trials were generally at high risk of bias. There is an overall high risk of performance bias due to lack of blinding of women and staff. Two studies were also at high risk of selection bias. We used GRADEpro software to grade evidence for our selected outcomes; for caesarean section we rated the evidence low quality and all the other outcomes (perinatal mortality, wound sepsis, blood transfusion, scar dehiscence and admission to special care baby unit) as very low quality. Downgrading was due to risk of bias relating to lack of allocation concealment and blinding, and imprecision of effect estimates. Women undergoing X-ray pelvimetry were more likely to have a caesarean section (risk ratio (RR) 1.34, 95% confidence interval (CI) 1.19 to 1.52; 1159 women; 5 studies; low-quality evidence). There were no clear differences between groups for perinatal outcomes: perinatal mortality (RR 0.53, 95% CI 0.19 to 1.45; 1159 infants; 5 studies; very low-quality evidence), perinatal asphyxia (RR 0.66, 95% CI 0.39 to 1.10; 305 infants; 1 study), and admission to special care baby unit (RR 0.20, 95% CI 0.01 to 4.13; 288 infants; 1 study; very low-quality evidence). Other outcomes assessed were wound sepsis (RR 0.83, 95% CI 0.26 to 2.67; 288 women; 1 study; very low-quality evidence), blood transfusion (RR 1.00, 95% CI 0.39 to 2.59; 288 women; 1 study; very low-quality evidence), and scar dehiscence (RR 0.59, 95% CI 0.14 to 2.46; 390 women; 2 studies; very low-quality evidence). Again, no clear differences were found for these outcomes between the women who received X-ray pelvimetry and those who did not. Apgar score less than seven at five minutes was not reported in any study. X-ray pelvimetry versus no pelvimetry or clinical pelvimetry is the only comparison included in this review due to the lack of trials identified that used other types or pelvimetry (other radiological examination or clinical pelvimetry versus no pelvimetry). There is not enough evidence to support the use of X-ray pelvimetry for deciding on mode of delivery in women whose fetuses have a cephalic presentation. Women who undergo an X-ray pelvimetry may be more likely to have a caesarean section. Further research should be directed towards defining whether there are specific clinical situations in which pelvimetry can be shown to be of value. Newer methods of pelvimetry (CT, MRI) should be subjected to randomised trials to assess their value. Further trials of X-ray pelvimetry in cephalic presentations would be of value if large enough to assess the effect on perinatal mortality.\n",
      "We searched for evidence on 30th November 2016 and identified five trials with a total of 1159 pregnant women. All five trials used X-ray pelvimetry in comparison to no X-ray pelvimetry. The women who received X-ray pelvimetry were more likely to have a caesarean section (low-quality evidence). Whether a woman had pelvimetry or not, we found no difference in the numbers of babies that died (very low-quality evidence), who did not have enough oxygen during labour, or were admitted to special care baby units (very low-quality evidence). For the women, no differences were found between numbers of women with wound sepsis, those who received a blood transfusion, or those whose caesarean section scar began to break down (all very low-quality evidence). Apgar score less than seven at five minutes was not reported in any study. There is too little evidence (the majority of which is low quality) to show whether measuring the size of the woman's pelvis (pelvimetry) is beneficial and safe when the baby is in a head-down position. The number of women having a caesarean section increased if women had X-ray pelvimetry but there was insufficient good-quality evidence to show if pelvimetry improves outcomes for the baby. More research is needed.\n",
      "\n",
      "\n",
      "Idx 100\n",
      "We included one study with 211 participants (median age 13 years), in which etanercept (dosage ranged from 0.8 to 50 mg per kilogram of body weight) was compared to placebo. Follow-up was over a 48-week period. At week 12, 57% versus 11% who received etanercept or placebo, respectively, achieved the PASI 75 (risk ratio 4.95, 95% confidence interval (CI) 2.83 to 8.65; high-quality evidence). Absolute risk reduction and the number needed to treat to obtain a benefit with etanercept was 45% (95% CI 33.95 to 56.40) and 2 (95% CI 1.77 to 2.95), respectively. The percentage improvement from baseline of the CDLQI scores at week 12 was better in the etanercept group than the placebo group (52.3% versus 17.5%, respectively (P = 0.0001)). Analysis between the groups showed an effect size that was clinically important (mean difference 2.30, 95% CI 0.85 to 3.75; high-quality evidence). However, means, medians, and minimal important difference results and results of the Pediatric Quality of Life Inventory, Stein Impact on Family Scale, and Harter Self-Perception Profile for Children scores must be interpreted with caution, as they were not prespecified outcomes. Three serious adverse events were reported, but they were resolved without sequelae. Deaths or other events such as malignant tumours, opportunistic infections, tuberculosis, or demyelination were not reported in the included study. Also, 13% of participants in the placebo group and 53% in the etanercept group had a PGA of clear or almost clear (risk ratio 3.96, 95% CI 2.36 to 6.66; high-quality evidence) at week 12. This review found only one RCT evaluating the use of this type of biological therapy. Although the risk of publication bias was high, as we included only one industry-sponsored RCT, the risk of allocation, selection, performance, attrition, and selective reporting biases for all outcomes (except for CDLQI) was low, and no short-term serious adverse events were found. We can conclude, based on this single included study, that etanercept seems to be efficacious and safe (at least in the short term) for the treatment of paediatric psoriasis. However, as the GRADE approach refers not to individual studies but to a body of evidence, we shall wait for the results of the ongoing studies in a future update of this review. In addition, future studies should evaluate quality-of-life endpoints established a priori and standardise primary outcome measures such as PASI 75, and should include the PGA as a secondary endpoint. Also, collating and reporting adverse events uniformly is required to better evaluate safety.\n",
      "We searched for all randomised controlled trials (RCTs) that assessed the efficacy and safety of anti-TNF agents for the treatment of long-term plaque psoriasis in individuals younger than 18 years of age. We searched databases up to July 2015. Only one study (with three phases: a 12-week randomised, double-blind, placebo-controlled phase; a 24-week open-label phase, and a 12-week phase of a randomised, double-blind, withdrawal–retreatment design) investigating one anti-TNF agent (etanercept) in 211 participants met the inclusion criteria. Evidence from this single included study suggests that by week 12 etanercept reduced the extent of the psoriasis in children when compared with placebo. Although a few adverse events were reported, they were resolved without subsequent problems. We did not find any evidence on long-term side effects of this drug from this included study. Although this one RCT provided high-quality evidence for the Physician's Global Assessment and all Psoriasis Area and Severity Index scores (75, 90, and 50) and moderate-quality evidence for quality-of-life outcomes, we found no further randomised studies either evaluating etanercept or comparing other anti-TNF agents, highlighting the need for further well-designed randomised studies involving the use of biological therapies in children and young people with psoriasis. Several studies are ongoing that have not yet been completed or published. We plan to include the results of these in future updates of this review.\n",
      "\n",
      "\n",
      "Idx 101\n",
      "The search retrieved 126 trials; 10 fulfilled the inclusion criteria and we included them in the review (a total sample of 510 participants). Seven studies were considered to have low risk of bias, and three were considered as high risk of bias. A total of six trials compared Pilates to minimal intervention. There is low quality evidence that Pilates reduces pain compared with minimal intervention, with a medium effect size at short-term follow-up (less than three months after randomisation) (MD -14.05, 95% confidence interval (CI) -18.91 to -9.19). For intermediate-term follow-up (at least three months but less than 12 months after randomisation), two trials provided moderate quality evidence that Pilates reduces pain compared to minimal intervention, with a medium effect size (MD -10.54, 95% CI -18.46 to -2.62). Based on five trials, there is low quality evidence that Pilates improves disability compared with minimal intervention, with a small effect size at short-term follow-up (MD -7.95, 95% CI -13.23 to -2.67), and moderate quality evidence for an intermediate-term effect with a medium effect size (MD -11.17, 95% CI -18.41 to -3.92). Based on one trial and low quality evidence, a significant short-term effect with a small effect size was reported for function (MD 1.10, 95% CI 0.23 to 1.97) and global impression of recovery (MD 1.50, 95% CI 0.70 to 2.30), but not at intermediate-term follow-up for either outcome. Four trials compared Pilates to other exercises. For the outcome pain, we presented the results as a narrative synthesis due to the high level of heterogeneity. At short-term follow-up, based on low quality evidence, two trials demonstrated a significant effect in favour of Pilates and one trial did not find a significant difference. At intermediate-term follow-up, based on low quality evidence, one trial reported a significant effect in favour of Pilates, and one trial reported a non-significant difference for this comparison. For disability, there is moderate quality evidence that there is no significant difference between Pilates and other exercise either in the short term (MD -3.29, 95% CI -6.82 to 0.24) or in the intermediate term (MD -0.91, 95% CI -5.02 to 3.20) based on two studies for each comparison. Based on low quality evidence and one trial, there was no significant difference in function between Pilates and other exercises at short-term follow-up (MD 0.10, 95% CI -2.44 to 2.64), but there was a significant effect in favour of other exercises for intermediate-term function, with a small effect size (MD -3.60, 95% CI -7.00 to -0.20). Global impression of recovery was not assessed in this comparison and none of the trials included quality of life outcomes. Two trials assessed adverse events in this review, one did not find any adverse events, and another reported minor events. We did not find any high quality evidence for any of the treatment comparisons, outcomes or follow-up periods investigated. However, there is low to moderate quality evidence that Pilates is more effective than minimal intervention for pain and disability. When Pilates was compared with other exercises we found a small effect for function at intermediate-term follow-up. Thus, while there is some evidence for the effectiveness of Pilates for low back pain, there is no conclusive evidence that it is superior to other forms of exercises. The decision to use Pilates for low back pain may be based on the patient's or care provider's preferences, and costs.\n",
      "This review included 10 studies and 510 patients. All studies included a similar population of people with non-specific low back pain. The studies only included participants with chronic low back pain. The duration of the treatment programmes in the included trials ranged from 10 days to 90 days. The duration of follow-up varied from four weeks to six months. None of the included studies measured follow-up beyond six months. The sample sizes ranged from 17 to 87 participants. The included studies demonstrated that Pilates is probably more effective than minimal intervention in the short and intermediate term for pain and disability outcomes, and more effective than minimal intervention for improvement in function and global impression of recovery in the short term. Pilates is probably not more effective than other exercises for pain and disability in the short and intermediate term. For function, other exercises were more effective than Pilates at intermediate-term follow-up, but not at short-term follow-up. Thus, while there is some evidence for the effectiveness of Pilates for low back pain, there is no conclusive evidence that it is superior to other forms of exercise. Minor or no adverse events were reported for the interventions in this review. The overall quality of the evidence in this review ranged from low to moderate.\n",
      "\n",
      "\n"
     ]
    }
   ],
   "source": [
    "dataset_labels = [x[\"labels\"][0] for x in dataset[\"train\"]]\n",
    "dataset_inputs = [x[\"input\"] for x in dataset[\"train\"]]\n",
    "\n",
    "for idx, item in enumerate(zip(dataset_inputs, dataset_labels)):\n",
    "    print(f\"Idx {idx+1}\")\n",
    "    print(item[0])\n",
    "    print(item[1])\n",
    "    print(\"\\n\")\n",
    "    if idx>99:\n",
    "        break"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 22,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/home/lyf6/miniconda3/envs/simplification/lib/python3.8/site-packages/sklearn/base.py:318: UserWarning: Trying to unpickle estimator TfidfTransformer from version 1.1.2 when using version 1.2.2. This might lead to breaking code or invalid results. Use at your own risk. For more info please refer to:\n",
      "https://scikit-learn.org/stable/model_persistence.html#security-maintainability-limitations\n",
      "  warnings.warn(\n",
      "/home/lyf6/miniconda3/envs/simplification/lib/python3.8/site-packages/sklearn/base.py:318: UserWarning: Trying to unpickle estimator TfidfVectorizer from version 1.1.2 when using version 1.2.2. This might lead to breaking code or invalid results. Use at your own risk. For more info please refer to:\n",
      "https://scikit-learn.org/stable/model_persistence.html#security-maintainability-limitations\n",
      "  warnings.warn(\n"
     ]
    },
    {
     "data": {
      "text/plain": [
       "{'check_entities': '96/100',\n",
       " 'check_entities_ents': [['ulcers',\n",
       "   'second',\n",
       "   'growth factors',\n",
       "   'january 2019',\n",
       "   '49',\n",
       "   'only two',\n",
       "   'arterial disease'],\n",
       "  ['carotid artery narrowing',\n",
       "   '26 january 2016',\n",
       "   '47 to 84 years',\n",
       "   'surgical treatment'],\n",
       "  ['only three', 'bowel', 'advanced cancer'],\n",
       "  ['first', 'third', 'second'],\n",
       "  ['treatments',\n",
       "   'combined radiotherapy',\n",
       "   'pleural mesothelioma',\n",
       "   'up to 21 march 2017',\n",
       "   'primary pleural cancer'],\n",
       "  ['blood antibodies',\n",
       "   '1358',\n",
       "   'prenatal class',\n",
       "   '10-minute',\n",
       "   'third',\n",
       "   '2790',\n",
       "   '22.4%',\n",
       "   'only 5%',\n",
       "   '2591',\n",
       "   'toxoplasmosis infection',\n",
       "   'four',\n",
       "   '285',\n",
       "   '13'],\n",
       "  ['the first two years',\n",
       "   'two',\n",
       "   'analysis',\n",
       "   'injection site reactions',\n",
       "   'flu-like',\n",
       "   'only\\xa0 ',\n",
       "   'ifn beta therapy'],\n",
       "  ['intervention',\n",
       "   'between 36 and 79',\n",
       "   'between 65',\n",
       "   'cvd',\n",
       "   '4.2 years',\n",
       "   'harmful',\n",
       "   'between 457 and 553',\n",
       "   'only two',\n",
       "   'july 2019',\n",
       "   'between 2 years'],\n",
       "  ['second', 'two'],\n",
       "  ['adrenergic drugs',\n",
       "   '22',\n",
       "   'seven',\n",
       "   'high blood pressure',\n",
       "   'urinary incontinence',\n",
       "   'stress incontinence',\n",
       "   'muscle exercises'],\n",
       "  ['only one', 'august 2016', 'african americans', '1693'],\n",
       "  ['58%',\n",
       "   '58 years',\n",
       "   'analgesic medications',\n",
       "   'critically ill',\n",
       "   'one 20 to',\n",
       "   'methodological weakness',\n",
       "   'harm',\n",
       "   '30-minute',\n",
       "   'oxygen saturation level',\n",
       "   'mechanical ventilation'],\n",
       "  ['february 2017',\n",
       "   'chinese',\n",
       "   'two',\n",
       "   'acupuncture procedure',\n",
       "   'april 2017',\n",
       "   '14'],\n",
       "  ['stomach', 'between 7% and 14%', 'august 2016', 'active treatment'],\n",
       "  ['no intervention',\n",
       "   'hsv-2',\n",
       "   'september 2013',\n",
       "   'preventing',\n",
       "   'herpes',\n",
       "   'sti tests'],\n",
       "  ['rather than two', 'limbs', 'limb', 'two'],\n",
       "  ['6 or 12 months',\n",
       "   'disease',\n",
       "   'methotrexate',\n",
       "   'six to twelve month',\n",
       "   'pain',\n",
       "   'anti-rheumatic drug',\n",
       "   'tumour necrosis factor alpha',\n",
       "   'ra'],\n",
       "  ['the past 14 years'],\n",
       "  ['cbas'],\n",
       "  ['759',\n",
       "   'two',\n",
       "   'medicines',\n",
       "   'hormone',\n",
       "   'prostaglandin',\n",
       "   'one',\n",
       "   'only nine',\n",
       "   '19'],\n",
       "  ['9',\n",
       "   '24',\n",
       "   'treatments',\n",
       "   'side effect',\n",
       "   'painkillers',\n",
       "   'october 2015',\n",
       "   'about 10',\n",
       "   '59',\n",
       "   'about 6000',\n",
       "   '100',\n",
       "   '500 mg',\n",
       "   '49',\n",
       "   'paracetamol 1000 mg',\n",
       "   'international headache',\n",
       "   '19',\n",
       "   'medicine'],\n",
       "  ['cochrane',\n",
       "   'cochrane schizophrenia',\n",
       "   'antipsychotic dose',\n",
       "   'antipsychotic drug',\n",
       "   'up to 30 march 2017',\n",
       "   '1919',\n",
       "   'antipsychotic treatment'],\n",
       "  ['stomach',\n",
       "   '2015',\n",
       "   'intestine',\n",
       "   'miniature drug capsules',\n",
       "   'tablets',\n",
       "   'sudy',\n",
       "   'medication',\n",
       "   'body mass index',\n",
       "   '1986',\n",
       "   'factors',\n",
       "   'toilet',\n",
       "   'microspheres',\n",
       "   '13',\n",
       "   'enteric-coated'],\n",
       "  ['the number of days', 'analysis', 'oral antibiotics'],\n",
       "  ['delivery',\n",
       "   'two',\n",
       "   'the united states',\n",
       "   'less than half',\n",
       "   'two weeks',\n",
       "   '1998-1999'],\n",
       "  ['two',\n",
       "   'finding',\n",
       "   'six',\n",
       "   'brief advice',\n",
       "   'up to 18 july 2018',\n",
       "   'at least six months'],\n",
       "  ['tumour', 'september 2019'],\n",
       "  ['3',\n",
       "   '2013',\n",
       "   'treatments',\n",
       "   'ages',\n",
       "   'four to six weeks later',\n",
       "   'two weeks to one year',\n",
       "   'a zero',\n",
       "   'two hours to 12 months',\n",
       "   '1',\n",
       "   '100',\n",
       "   'between the ages of 18 and 65 years',\n",
       "   'scale',\n",
       "   '56',\n",
       "   'six to 12 weeks',\n",
       "   'half'],\n",
       "  ['65 years old',\n",
       "   'between six months',\n",
       "   'stop',\n",
       "   'august 2016',\n",
       "   'seventeen',\n",
       "   'placebo',\n",
       "   'five years',\n",
       "   'stroke',\n",
       "   '18%',\n",
       "   'drug',\n",
       "   'heart attack'],\n",
       "  ['kidney transplant',\n",
       "   'antibiotic',\n",
       "   'urinary tract infections',\n",
       "   'urological complications',\n",
       "   'prevention'],\n",
       "  ['calf muscle', 'prevent', 'muscle cramp', 'only one'],\n",
       "  ['2015',\n",
       "   'two hours to 10 days',\n",
       "   'lungs',\n",
       "   'eleven',\n",
       "   'two',\n",
       "   'clot',\n",
       "   'breathlessness',\n",
       "   'brain swelling',\n",
       "   'ten',\n",
       "   'complication',\n",
       "   'ischaemic stroke',\n",
       "   'bleed',\n",
       "   'one',\n",
       "   'haemorrhagic stroke',\n",
       "   'excess',\n",
       "   'lung infection'],\n",
       "  ['budesonide', 'reliever formoterol'],\n",
       "  ['six hour', '9 hours', 'adverse event', 'postoperative pain'],\n",
       "  ['up to 23 january 2018',\n",
       "   'only 48%',\n",
       "   'cochrane',\n",
       "   'treatments',\n",
       "   'monitored',\n",
       "   'treated with',\n",
       "   '1 year',\n",
       "   'dental decay',\n",
       "   'placebo beads',\n",
       "   'gel',\n",
       "   'analysis',\n",
       "   'placebo',\n",
       "   'toothpaste',\n",
       "   'mouthrinse',\n",
       "   'a minimum of',\n",
       "   'one'],\n",
       "  ['at least 24 months',\n",
       "   'eye',\n",
       "   'procedure',\n",
       "   'limbal surgery',\n",
       "   'medications',\n",
       "   'operation',\n",
       "   '23 october 2015'],\n",
       "  ['six months',\n",
       "   'plan',\n",
       "   '12 months',\n",
       "   'august 2015',\n",
       "   'years',\n",
       "   'antiviral medication',\n",
       "   'weeks',\n",
       "   '12-day',\n",
       "   'two to four days'],\n",
       "  ['intervention',\n",
       "   'adverse events',\n",
       "   'herbal therapy',\n",
       "   '2334',\n",
       "   'side-effects',\n",
       "   'twenty four'],\n",
       "  ['92',\n",
       "   'plcs',\n",
       "   'outbursts',\n",
       "   'uk',\n",
       "   '57.8 years to',\n",
       "   'denmark',\n",
       "   'europe',\n",
       "   'scotland',\n",
       "   '1',\n",
       "   'adverse event',\n",
       "   'sweden',\n",
       "   'japan',\n",
       "   'antidepressant',\n",
       "   'south korea',\n",
       "   '10',\n",
       "   'asia',\n",
       "   '73 years'],\n",
       "  ['prevent',\n",
       "   'complications',\n",
       "   'operation',\n",
       "   'glaucoma',\n",
       "   'glaucoma surgery',\n",
       "   'cataracts'],\n",
       "  ['surfactant', 'chronic lung disease', 'one', 'mechanical ventilation'],\n",
       "  ['intervention',\n",
       "   'blood clot',\n",
       "   'haemostatic agents',\n",
       "   '18 years old',\n",
       "   'blood test',\n",
       "   '28 january 2019',\n",
       "   '30 days',\n",
       "   'only two',\n",
       "   'blood transfusions',\n",
       "   'non-cardiac operations',\n",
       "   'blood tests'],\n",
       "  ['chronic skin disease',\n",
       "   'european',\n",
       "   'ten',\n",
       "   'salicylic',\n",
       "   'oil',\n",
       "   'about 50%',\n",
       "   '5',\n",
       "   'grenz ray',\n",
       "   'hyaluronic acid',\n",
       "   '5-fluorouracil',\n",
       "   'uvb',\n",
       "   '2% to 3%',\n",
       "   'dithranol',\n",
       "   'chondroitin',\n",
       "   'salicylic and uvb',\n",
       "   'grenz rays.',\n",
       "   'readers',\n",
       "   '50 mg and',\n",
       "   'skin psoriasis'],\n",
       "  [],\n",
       "  ['9,946',\n",
       "   '3',\n",
       "   '9',\n",
       "   'rheumatoid arthritis',\n",
       "   'up to 1 april 2014',\n",
       "   'gold',\n",
       "   '4,682',\n",
       "   'scale',\n",
       "   '19'],\n",
       "  ['evening',\n",
       "   'caesarian section',\n",
       "   'morning',\n",
       "   'only three',\n",
       "   'shortens',\n",
       "   'cervix',\n",
       "   'epidural anaesthesia',\n",
       "   'hormones'],\n",
       "  ['teb',\n",
       "   'open thoracotomy',\n",
       "   'acute pain control',\n",
       "   'only one',\n",
       "   'vomiting',\n",
       "   'pain control',\n",
       "   'medications',\n",
       "   'itching',\n",
       "   '30 days',\n",
       "   'five days',\n",
       "   'only two',\n",
       "   'nausea'],\n",
       "  ['july 2013', 'one year', 'spectacles'],\n",
       "  ['re-operation',\n",
       "   '2004',\n",
       "   'anastomotic leak',\n",
       "   'anastomotic drainage',\n",
       "   'colorectal anastomosis',\n",
       "   'analysis',\n",
       "   'germany',\n",
       "   'anastomotic',\n",
       "   'france',\n",
       "   'anastomotic leak,',\n",
       "   'february 2015'],\n",
       "  ['infection', '16 june 2015', 'dermatitis', 'age 61 years'],\n",
       "  ['12', '11'],\n",
       "  ['104',\n",
       "   'only 19%',\n",
       "   'sixteen',\n",
       "   'five',\n",
       "   '20',\n",
       "   'two',\n",
       "   '51.6 to 69 years',\n",
       "   'seven',\n",
       "   'heart disease',\n",
       "   'one',\n",
       "   'coronary heart disease',\n",
       "   'four',\n",
       "   '10',\n",
       "   '525',\n",
       "   'heart attack'],\n",
       "  ['prevent',\n",
       "   'treatments',\n",
       "   'treated with',\n",
       "   'analysis',\n",
       "   'prophylactic treatment',\n",
       "   '73%'],\n",
       "  ['approximately two days', '50', 'two'],\n",
       "  ['4 weeks',\n",
       "   'adjunct',\n",
       "   'analysis',\n",
       "   'only seven',\n",
       "   'pain control',\n",
       "   'baseline',\n",
       "   'january 2016',\n",
       "   'monitor',\n",
       "   'depressive mood'],\n",
       "  ['sixteen',\n",
       "   'impair',\n",
       "   'endoscopy',\n",
       "   'diagnose',\n",
       "   'portal vein',\n",
       "   '15%',\n",
       "   'october 2013',\n",
       "   'portal vein thrombosis',\n",
       "   'chronic liver disease',\n",
       "   'about 15%'],\n",
       "  ['prevention', 'drug'],\n",
       "  ['ttm', 'medications'],\n",
       "  ['steroids', 'metered-dose inhalers', 'spacers', 'inhaler'],\n",
       "  ['eight',\n",
       "   'corticosteroid',\n",
       "   'tablets',\n",
       "   'systemic corticosteroid therapy',\n",
       "   'imaging studies',\n",
       "   'mechanically ventilated',\n",
       "   'eighteen',\n",
       "   'non-severe'],\n",
       "  ['more than 28 days', 'adverse events', 'monthly', 'hormone'],\n",
       "  ['prevent',\n",
       "   'resecting',\n",
       "   'complication',\n",
       "   'primary cancer',\n",
       "   'surgically',\n",
       "   'cancer'],\n",
       "  ['transplantation', 'allogeneic hematopoeitic cell transplantation'],\n",
       "  ['obese', 'stomach disorders', 'a few hours', 'anaesthetic'],\n",
       "  ['second',\n",
       "   'vaginal skin',\n",
       "   'incontinence',\n",
       "   'complications',\n",
       "   'first',\n",
       "   'sexual discomfort'],\n",
       "  ['299',\n",
       "   'ftd',\n",
       "   '27',\n",
       "   'gamma cameras',\n",
       "   'today',\n",
       "   'tertiary',\n",
       "   'diagnosing',\n",
       "   '21-year',\n",
       "   '363',\n",
       "   'university clinics',\n",
       "   'june 2013'],\n",
       "  ['over 65 years'],\n",
       "  ['13 january 2015',\n",
       "   'layer',\n",
       "   'choroid',\n",
       "   'retina',\n",
       "   'procedure',\n",
       "   'separation',\n",
       "   '5 to 27 months',\n",
       "   'adverse events',\n",
       "   'surgeries',\n",
       "   'us',\n",
       "   'nearsightedness',\n",
       "   '6 months to 2 years',\n",
       "   'ocular adverse events',\n",
       "   'sclera'],\n",
       "  ['3',\n",
       "   'cardiorespiratory plus',\n",
       "   '2',\n",
       "   '1',\n",
       "   'health problems',\n",
       "   'february 2015'],\n",
       "  ['16',\n",
       "   'premature cardiovascular disease',\n",
       "   'therapies',\n",
       "   'premature heart disease',\n",
       "   'ckd',\n",
       "   'vitamin compounds'],\n",
       "  ['oral vaccines'],\n",
       "  ['drug hydroxyurea', 'captopril', 'protein', 'high blood pressure', 'drug'],\n",
       "  ['as low as 6 or as many as 28',\n",
       "   'as many as 80',\n",
       "   '54',\n",
       "   '0-100',\n",
       "   '95 percent',\n",
       "   'as little as 15',\n",
       "   'as little as 20',\n",
       "   '17',\n",
       "   'six weeks',\n",
       "   '12 weeks',\n",
       "   'as few as 4 or as many as 11',\n",
       "   'as many as 95',\n",
       "   '11',\n",
       "   '0-500'],\n",
       "  ['185',\n",
       "   'leg',\n",
       "   'uk',\n",
       "   '2014',\n",
       "   'breathing support',\n",
       "   'critically ill',\n",
       "   'longer than 24 hours',\n",
       "   'rehabilitation',\n",
       "   'italy',\n",
       "   'australia',\n",
       "   '298',\n",
       "   'the age of 18 years',\n",
       "   'mechanically ventilated',\n",
       "   'february 2015'],\n",
       "  ['surgical complications',\n",
       "   'treatments',\n",
       "   '0/226',\n",
       "   'analysis',\n",
       "   'complications',\n",
       "   'operation'],\n",
       "  ['prevent',\n",
       "   'monitored',\n",
       "   'platinum chemotherapy',\n",
       "   'bone cancer',\n",
       "   'drugs',\n",
       "   'medicines',\n",
       "   'liver cancer',\n",
       "   'more than four years',\n",
       "   'cancer',\n",
       "   'january 2019',\n",
       "   'medicine',\n",
       "   'half'],\n",
       "  ['genital warts', 'mcsa', 'laser treatment', '5-fu + infα-2a'],\n",
       "  ['diagnostic laparoscopy',\n",
       "   'detection',\n",
       "   'diagnostic surgery',\n",
       "   'ultrasound',\n",
       "   'april 2015',\n",
       "   'testing methods',\n",
       "   'diagnosing',\n",
       "   'diagnostic',\n",
       "   '11'],\n",
       "  ['three', 'treated with'],\n",
       "  ['disease progression',\n",
       "   'therapies',\n",
       "   'only one',\n",
       "   'first',\n",
       "   'monoclonal antibodies'],\n",
       "  ['antibiotic therapies', 'december 2014', 'hoarseness of voice'],\n",
       "  ['eleven',\n",
       "   'treatments',\n",
       "   'medicine',\n",
       "   'heroin',\n",
       "   '1759',\n",
       "   'drug use',\n",
       "   'august 2016',\n",
       "   'medicines',\n",
       "   'brief advice',\n",
       "   'behavioural support',\n",
       "   'twelve',\n",
       "   'substance abuse',\n",
       "   'at least six months'],\n",
       "  ['abdominal pain',\n",
       "   'blood sugar response',\n",
       "   'three months',\n",
       "   'only four',\n",
       "   'antidiabetic drugs',\n",
       "   'three',\n",
       "   'diarrhoea',\n",
       "   'four weeks'],\n",
       "  ['antiplatelet drugs',\n",
       "   'a few days',\n",
       "   'stop',\n",
       "   'six months',\n",
       "   'blood transfusion',\n",
       "   'january 2018',\n",
       "   'placebo',\n",
       "   'stopping',\n",
       "   'stroke',\n",
       "   'placebo agent',\n",
       "   'heart attack'],\n",
       "  ['2 to 44 months',\n",
       "   'no intervention',\n",
       "   'zinc',\n",
       "   'up to july 2019',\n",
       "   'only 2',\n",
       "   '22',\n",
       "   'under two years of age',\n",
       "   'vitamins',\n",
       "   'iron',\n",
       "   '6 to 23 months of age',\n",
       "   'six months to two years',\n",
       "   'vitamin'],\n",
       "  [],\n",
       "  ['non-medication treatments', 'measure pain', 'treatments'],\n",
       "  ['swelling',\n",
       "   'cochrane',\n",
       "   'legs',\n",
       "   'mechanical neck disorders',\n",
       "   'neck pain',\n",
       "   'joint pain',\n",
       "   'hundreds',\n",
       "   'muscle activation exercises',\n",
       "   'january 2016',\n",
       "   'diagnoses',\n",
       "   'knee',\n",
       "   'muscle soreness',\n",
       "   'joint disease',\n",
       "   'period pain',\n",
       "   '10',\n",
       "   'polio'],\n",
       "  [],\n",
       "  [],\n",
       "  ['injections',\n",
       "   'disease',\n",
       "   'redness',\n",
       "   'antibody',\n",
       "   'fever',\n",
       "   'injection',\n",
       "   'antibody injections',\n",
       "   'only one',\n",
       "   'injecting antibodies',\n",
       "   'complications',\n",
       "   'catching',\n",
       "   'the modern day',\n",
       "   'antibodies',\n",
       "   'only two',\n",
       "   'august 2013'],\n",
       "  ['ovarian stimulation', 'april 2015', '1643', 'at least 14 days'],\n",
       "  ['12', 'eight'],\n",
       "  ['900 ppm f',\n",
       "   'filled teeth',\n",
       "   'between 1965 and 2005',\n",
       "   'supervision',\n",
       "   'treated with',\n",
       "   'more than 15,000',\n",
       "   'baby teeth',\n",
       "   'million',\n",
       "   'fluoride',\n",
       "   'placebo',\n",
       "   'six to 14 years',\n",
       "   'cope',\n",
       "   'from two to three years',\n",
       "   'mouthrinses',\n",
       "   'tooth decay',\n",
       "   'no mouthrinse'],\n",
       "  ['interferons',\n",
       "   'injections',\n",
       "   'muscle pain',\n",
       "   'joint pain',\n",
       "   'injection site reactions',\n",
       "   'one',\n",
       "   'ulcerative colitis',\n",
       "   'steroid drug'],\n",
       "  ['two consecutive days', 'prevention', 'december 2015'],\n",
       "  ['antifungal drug',\n",
       "   'suppression',\n",
       "   'eight',\n",
       "   'treated with',\n",
       "   'glucocorticoids',\n",
       "   'december 2016',\n",
       "   'hpa axis'],\n",
       "  ['oral methotrexate',\n",
       "   'therapies',\n",
       "   'imi gold',\n",
       "   'auranofin',\n",
       "   'parenteral methotrexate',\n",
       "   'over half',\n",
       "   'fumaric acid'],\n",
       "  ['apgar', 'oxygen', '30th november 2016'],\n",
       "  ['up to july 2015',\n",
       "   '90',\n",
       "   'plaque',\n",
       "   'plan',\n",
       "   'psoriasis',\n",
       "   'younger than 18 years of age',\n",
       "   'biological therapies',\n",
       "   '50',\n",
       "   'anti-tnf agents',\n",
       "   '24-week',\n",
       "   'drug',\n",
       "   'retreatment',\n",
       "   'anti-tnf agent',\n",
       "   '12-week']]}"
      ]
     },
     "execution_count": 22,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "compute_metrics(\n",
    "    sources = dataset_inputs[:100],\n",
    "    predictions = dataset_labels[:100],\n",
    "    labels = [[] for _ in range(100)],\n",
    "    metrics = [\"check_entities\"]\n",
    ")"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "* XSum: 83/100\n",
    "* CNN: 74/100\n",
    "* MedEasi: 80/100\n",
    "* ASSET: 14/100\n",
    "* Cochrane: 68/100"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Noisy Examples\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 21,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "'Two tourist buses have been destroyed by fire in a suspected arson attack in Belfast city centre.'"
      ]
     },
     "execution_count": 21,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "dataset_labels[1]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "{'input': 'A fire alarm went off at the Holiday Inn in Hope Street at about 04:20 BST on Saturday and guests were asked to leave the hotel.\\nAs they gathered outside they saw the two buses, parked side-by-side in the car park, engulfed by flames.\\nOne of the tour groups is from Germany, the other from China and Taiwan. It was their first night in Northern Ireland.\\nThe driver of one of the buses said many of the passengers had left personal belongings on board and these had been destroyed.\\nBoth groups have organised replacement coaches and will begin their tour of the north coast later than they had planned.\\nPolice have appealed for information about the attack.\\nInsp David Gibson said: \"It appears as though the fire started under one of the buses before spreading to the second.\\n\"While the exact cause is still under investigation, it is thought that the fire was started deliberately.\"',\n",
       " 'labels': ['Two tourist buses have been destroyed by fire in a suspected arson attack in Belfast city centre.'],\n",
       " 'id': '40143035'}"
      ]
     },
     "execution_count": 19,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "dataset[\"train\"][1]"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Reordering BRIO for Evaluation"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "tokenized_corpus = [doc.split(\" \") for doc in refs]\n",
    "bm25 = BM25Okapi(tokenized_corpus)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "0\n",
      "100\n",
      "200\n",
      "300\n",
      "400\n",
      "500\n",
      "600\n",
      "700\n",
      "800\n",
      "900\n",
      "1000\n",
      "1100\n",
      "1200\n",
      "1300\n",
      "1400\n",
      "1500\n",
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      "1800\n",
      "1900\n",
      "2000\n",
      "2100\n",
      "2200\n",
      "2300\n",
      "2400\n",
      "2500\n",
      "2600\n",
      "2700\n",
      "2800\n",
      "2900\n",
      "3000\n",
      "3100\n",
      "3200\n",
      "3300\n",
      "3400\n",
      "3500\n",
      "3600\n",
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      "3800\n",
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      "4000\n",
      "4100\n",
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      "4300\n",
      "4400\n",
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      "5000\n",
      "5100\n",
      "5200\n",
      "5300\n",
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      "5600\n",
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      "6000\n",
      "6100\n",
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      "6500\n",
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      "7000\n",
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      "7300\n",
      "7400\n",
      "7500\n",
      "7600\n",
      "7700\n",
      "7800\n",
      "7900\n",
      "8000\n",
      "8100\n",
      "8200\n",
      "8300\n",
      "8400\n",
      "8500\n",
      "8600\n",
      "8700\n",
      "8800\n",
      "8900\n",
      "9000\n",
      "9100\n",
      "9200\n",
      "9300\n",
      "9400\n",
      "9500\n",
      "9600\n",
      "9700\n",
      "9800\n",
      "9900\n",
      "10000\n",
      "10100\n",
      "10200\n",
      "10300\n",
      "10400\n",
      "10500\n",
      "10600\n",
      "10700\n",
      "10800\n",
      "10900\n",
      "11000\n",
      "11100\n",
      "11200\n",
      "11300\n"
     ]
    }
   ],
   "source": [
    "reordered_preds, reordered_idxs = [], []\n",
    "for i, s in enumerate(dataset_labels):\n",
    "    if i%100==0: print(i)\n",
    "    \n",
    "    match = bm25.get_top_n(s.split(), refs, n=1)\n",
    "    # match = process.extractOne(s, refs)\n",
    "    match_idx = refs_label_2_idx[match[0]]\n",
    "    pred = preds[match_idx]\n",
    "\n",
    "    # results = rouge.compute(predictions=[s]*len(refs),\n",
    "    #                         references=refs,\n",
    "    #                         use_aggregator=False,\n",
    "    #                         rouge_types=['rouge1'])\n",
    "    # match_idx = np.argmax(results[\"rouge1\"])\n",
    "    # pred = preds[match_idx]\n",
    "\n",
    "    reordered_preds.append(pred)\n",
    "    reordered_idxs.append(match_idx)\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Done\n"
     ]
    }
   ],
   "source": [
    "# Write output\n",
    "with open(f\"output/xsum.reordered.txt\", \"w\") as fp:\n",
    "    for item in reordered_preds:\n",
    "        fp.write(\"%s\\n\" % item)\n",
    "    print(\"Done\")"
   ]
  }
 ],
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